A Case of Calciphylaxis in a Patient with Hypoparathyroidism and Normal Renal Function

ObjectiveTo present the case of a patient with a history of thyroid cancer, postsurgical hypoparathyroidism, chronic calcitriol use, and normal renal function who presented with painful skin lesions secondary to calciphylaxis.MethodsWe describe the history, biochemistry, histopathology, evaluation, and management of this patient.ResultsA 47-year-old female with hypoparathyroidism, chronically treated with calcitriol and calcium, presented with exquisitely painful skin ulcerations. Four months prior to the onset of symptoms, she had initiated warfarin therapy for atrial fibrillation. Review of laboratory data from the past year revealed elevated calcium and phosphorus levels. A diagnosis of calciphylaxis was made based upon pathologic evaluation of a skin biopsy. Management included titration of calcitriol and calcium to maintain serum calcium and phosphate levels in the low-normal range. Sodium thiosulfate was administered at a dose of 25 mg intravenously 3 times a week with some resolution in the patient’s pain. Unfortunately, the patient battled recurrent bacteremia and sepsis, presumably related to her calciphylaxis wounds, and ultimately succumbed to complications from sepsis.ConclusionAlthough calciphylaxis is typically associated with renal insufficiency and secondary hyperparathyroidism, we highlight the case of a patient with normal renal function and hypoparathyroidism. Patients treated with chronic calcitriol should have serum calcium and phosphorus monitored closely and may benefit from non– calcium-based phosphate binders if hyperphosphatemia becomes unavoidable. This is especially important in the presence of other risk factors for calciphylaxis, including warfarin use. (Endocr Pract. 2014;20:e102-e105)     

Unusual Case of Calciphylaxis Associated with Primary Hyperparathyroidism Without Coexistent Renal Failure

ObjectiveTo report a case of calciphylaxis in a patient with primary hyperparathyroidism without coexistent renal failure.MethodsThe clinical, laboratory, and radiographic details of this case are reviewed, and the pathogenesis of calciphylaxis and the associated prognosis are discussed.ResultsA 52-year-old woman had progressive fatigue, cachexia, severe osteoporosis, and necrotizing skin lesions. Her serum calcium level was 16 mg/dL, serum phosphorus level was 2.13 mg/dL, and parathyroid hormone level was 2,257 pg/mL (reference range, 15 to 65). On physical examination, gangrenous skin lesions with black crusts were noted on her legs, abdomen, and gluteal region. A mass lesion was detected in the parathyroid region by both ultrasonography and a parathyroid scan. The patient underwent a bilateral neck exploration, and a parathyroid adenoma measuring 3.5 by 1.5 by 1.2 cm was found on pathologic examination. After the operation, biochemical findings normalized, and the skin lesions progressively improved.ConclusionSevere primary hyperparathyroidism may be a factor leading to calciphylaxis, even in the absence of renal failure and a high calcium-phosphate product. This potentially life-threatening condition should not be left untreated if the levels of serum calcium and parathyroid hormone are severely elevated. (Endocr Pract. 2008;14:368-372)     

Hypercalcemia and Acromegaly-Clarifying the Connections: A Case Report and Review of the Literature

ObjectiveHypercalcemia in patients with acromegaly is rare and usually due to co-existent primary hyperparathyroidism. The etiology of hypercalcemia directly related to acromegaly is debated.MethodsWe present a case report of 1,25(OH)2D3-mediated hypercalcemia in a patient with acromegaly and discuss potential pathophysiological mechanisms contributing to the development of hypercalcemia late in the course of the disease.ResultsA 67-year-old female presented with classical features of acromegaly. A review of her previous photographs suggested a disease duration of approximately 10 years, and her serum calcium (Ca) was normal during this period. A biochemical work up confirmed a combined growth hormone (GH-) and prolactin (PRL-) cosecreting tumor with a GH level of 92.03 ng/mL (normal 0-3.61), an insulin-like growth factor-1 (IGF-1) level of 1,498 ng/ mL (59-225), and a PRL level of 223.3 ng/mL (2-17.4). Magnetic resonance imaging (MRI) of the pituitary showed a 1.9-cm macroadenoma. Her preoperative work up revealed new onset hypercalcemia with a corrected serum Ca level of 10.7 mg/dL (8.5-10.5), an ionized Ca level of 1.37 mmol/L (1.08-1.30), a parathyroid hormone (PTH) level of 13.0 pg/mL (10-60), and a high 1,25(OH)2D3 level of 72.6 pg/mL (15-60). She underwent resection of the pituitary adenoma with normalization of GH and PRL levels, and her IGF-1 level decreased to 304 ng/mL. Her serum Ca (9.3 mg/dL), ionized Ca(1.22) and 1,25(OH)2D3 levels (38.6 pg/mL) normalized after surgery.ConclusionWhile overt hypercalcemia in acromegaly is rare, it tends to occur late in the disease course. The hypercalcemia is mediated by elevated 1,25(OH)2D3 levels rather than PTH. (Endocr Pract. 2014;20:e86-e90)     

Addison’S Disease in Evolution: An Illustrative Case and Literature Review

ObjectiveTo present a case of symptomatic autoimmune adrenal insufficiency with initially normal serum cortisol and to caution about limitations of the current diagnostic algorithm for adrenal insufficiency, which does not reflect the pathophysiology of early disease.MethodsWe describe the clinical presentation and relevant investigations of a patient ultimately found to have Addison’s disease, which is followed by a focused review of the literature.ResultsA 41-year-old Caucasian woman with autoimmune hypothyroidism, premature ovarian failure, and microscopic colitis presented with nausea, salt craving, increased skin pigmentation, and postural hypotension. Initial bloodwork revealed a normal morning cortisol of level of 19.2 μg/dL (normal, 7.2 to 25 μg/dL) but an adrenocorticotropic hormone (ACTH) level 10 times normal, at 513.6 pg/mL (normal, < 52.5 pg/mL). Her potassium was normal, but her aldosterone level was 4.12 ng/dL (normal, 12.3 to 62.5 ng/dL) and her renin activity was increased (23.0 mg/dL/hour; normal, < 6.0 mg/dL/hour). Six weeks after initial presentation, she was found to have anti-adrenal antibodies. It was not until 10 weeks after her initial symptomatic presentation that her morning cortisol level was found to be subnormal and a formal diagnosis of adrenal insufficiency was made.ConclusionThe present case and literature review reveal that common diagnostic approaches will miss patients with (possibly symptomatic) early adrenal insufficiency. We suggest that serum ACTH level testing or tests of mineralocorticoid function be included in the initial step of investigation for suspected primary adrenal insufficiency. (Endocr Pract. 2014;20:e176-e179)     

Subacute thyroiditis manifesting as a thyroid mass, vocal cord paralysis, and hypercalcemia

ObjectiveTo report a case of subacute thyroiditis manifesting as a thyroid mass, vocal cord paralysis, and hypercalcemia.MethodsWe describe the clinical, laboratory, and radiologic findings in a patient with an unusual clinical course of subacute thyroiditis.ResultsA 65-year-old woman presented with a hoarse voice and an enlarging tender mass in the right side of the neck. On admission, thyroid function was consistent with thyrotoxicosis from subacute thyroiditis. Laboratory studies showed a corrected serum calcium concentration of 11.4 mg/dL, intact parathyroid hormone of 125 pg/mL, 25-hydroxyvitamin D of 12 ng/mL, and creatinine of 1.8 mg/dL. Computed tomography of the neck without use of a contrast agent showed a heterogeneous mass in the right side of the neck in conjunction with deviation of the trachea from right to left but without invasion of the trachea. Thyroid ultrasonography disclosed a heterogeneous mass in the right thyroid lobe measuring 4.7 cm by 5.5 cm by 4.5 cm. Flexible laryngoscopy revealed right vocal cord paralysis. Treatment with a course of prednisone yielded normalization of the serum calcium level, improvement in her voice, and a decrease in size of the thyroid mass. Four months after initial presentation of the patient, thyroid hormone levels became normal, she was clinically euthyroid, and she had a full recovery of her voice. Her serum calcium concentration was normal (9.8 mg/dL) in association with a near-normal parathyroid hormone level of 90 pg/mL. The 25-hydroxyvitamin D and creatinine values were also normal. Repeated thyroid ultrasonography showed a smaller right thyroid lobe with a dominant nodule measuring 2.0 cm by 1.3 cm by 1.4 cm in the right upper pole.ConclusionThis case illustrates that subacute thyroiditis can have the unusual initial manifestations of a thyroid mass, vocal cord paralysis, and hypercalcemia. In similar patients, a trial of corticosteroid therapy may be warranted in an effort to improve clinical symptoms and thus avoid unnecessary surgical treatment. (Endocr Pract. 2012;18:e17-e20)     

Unusual Recurrence of Hypercalcemia Due to Concurrent Parathyroid Adenoma and Parathyroid Sarcoidosis with Lymph Node Involvement

ObjectiveTo describe a patient presenting with the rare findings of synchronous parathyroid adenoma and parathyroid sarcoidosis.MethodsWe describe the clinical history, physical examination findings, laboratory values, imaging findings, and pathologic data of a man who developed recurrent se- vere hypercalcemia after successful parathyroidectomy.ResultsA 67-year-old man had the following initial blood test results: calcium, 11.1 mg/dL (reference range, 8.5-10.6 mg/dL); albumin 4.0 g/dL (reference range, 3.2-5.2 g/dL); intact parathyroid hormone, 166 pg/mL (refer- ence range, 10-69 pg/mL); creatinine, 1.9 mg/dL; 25-hy- droxyvitamin D, 15 ng/mL (reference range, 30-80 ng/ mL); and 1, 25-dihydroxyvitamin D, 44 pg/mL (reference range, 16-72 pg/mL). Chest x-ray was normal, and delayed images from a technetium Tc 99m sestamibi scan showed increased activity in the right lower pole of the thyroid. Two months after successful parathyroidectomy, the pa- tient was admitted to the hospital with a serum calcium concentration of 17 mg/dL. Pathologic examination of the resected gland confirmed the diagnosis of parathyroid ad- enoma, and subsequent review disclosed the presence of noncaseating granulomas within the adenoma.ConclusionsSarcoidosis with parathyroid involve- ment causing severe hypercalcemia is unique to this case.Recurrent hypercalcemia after successful resection of a parathyroid adenoma may require consideration of poten- tial causes other than the initial diagnosis. (Endocr Pract. 2010;16:463-467)     

Oncogenic Osteomalacia Cured by Removal of an Organized Hematoma

ObjectiveTo describe a patient with oncogenic osteomalacia whose symptoms were rapidly resolved after surgical removal of an organized hematoma of the hip.MethodsA case report is presented, including clinical and laboratory findings. The relevant literature is reviewed, and the current understanding of oncogenic osteomalacia is summarized.ResultsIn September 1996, a 44-year-old black woman presented with a 2-year history of bone pain, progressive muscle weakness, depression, osteomalacia, and hypophosphatemia. Her condition did not improve with use of calcitriol and phosphate replacement. During the previous year, her serum phosphorus levels were low, ranging from 1.0 to 2.2 mg/dL, and the levels of serum 1,25-dihydroxyvitamin D [1,25-(OH)₂D] were very low, ranging from < 5 to 19.4 pg/mL (normal, 15 to 60). The serum 25-hydroxyvitamin D levels were low, ranging from 8 to 14 ng/mL (normal, 9 to 52). The higher values were noted after she had received large doses of phosphate, 1,25-(OH)₂D, and vitamin D. During the previous year, her serum alkaline phosphatase levels were high, ranging from 253 to 314 U/L; serum calcium and parathyroid hormone levels were normal. The abnormalities on physical examination were obesity and a 10- by 10-cm firm, poorly demarcated mass superior to the left greater trochanter. A computed tomographic scan of this region showed a water-density fluid collection in the left buttock measuring 7.8 by 7.8 cm, consistent with a chronic hematoma. The mass was resected, and histopathologic examination revealed features of an organized hematoma with areas of myxoid changes and cartilaginous metaplasia. Postoperatively, the patient’s strength improved, and the levels of serum phosphorus and 1,25-(OH)₂D became supranormal.ConclusionThe symptoms and laboratory abnormalities of this patient with oncogenic osteomalacia promptly resolved after resection of an organized hematoma of the left hip. (Endocr Pract. 2005;11:190-193)     

Hypercalcemia Secondary to Gastrointestinal Stromal Tumors: Parathyroid Hormone-Related Protein Independent Mechanism?

ObjectiveHypercalcemia is a common paraneoplastic manifestation of many malignancies like breast, ovarian, and squamous-cell cancers of head and neck; however, there have been only a few case reports of hypercalcemia associated with gastrointestinal stromal tumors (GISTs). We report a case of GIST presenting with hypercalcemia without any osseous metastasis and provide a literature review regarding the mechanisms of hypercalcemia and therapeutic strategies.MethodsWe present a report of case and a review of the relevant literature.ResultsA 52-year-old woman with history of localized breast cancer in remission and a pelvic 13 × 12 cm GIST with peritoneal, liver, and lung metastases presented with hypercalcemia of 14.3 mg/dL (8.5-10.5 mg/dL). Parathyroid hormone-related protein (PTHrP) was undetectable, intact parathyroid hormone (PTH) was appropriately low at 1 pg/mL (10-65 pg/mL), and 1,25 dihydroxy vitamin D (1,25 OH₂ vit D) was elevated at 131 pg/mL (18-78 pg/mL) with normal renal function. Calcium responded transiently to tyrosine kinase inhibitor therapy and bisphosphonates but within a year, she expired due to tumor progression.ConclusionGIST is a rare cause of hypercalcemia. In addition to PTHrP expression, direct tumor production of 1,25(OH)₂ vit D or 1-α hydroxylase enzyme resulting in activation of 25-hydroxy vitamin D may be an alternative mechanism in GIST-related hypercalcemia. Therapy with tyrosine kinase inhibitors and bisphosphonates is recommended, though prognosis is poor. Further investigations are needed to characterize the etiology and management of hypercalcemia in these patients. (Endocr. Pract. 2013;19: e158-e162)     

Atypical Clinical Presentation of Acth-Dependent Cushing's Syndrome in a Patient Treated with Retinoic Acid

ObjectiveThe leading signs and symptoms of Cushing’s syndrome (CS) in adolescents, which depend on the duration and the severity of hypercortisolemia, are: a decrease in growth velocity with an increase in body weight, redistribution of fat tissue (round face), and less commonly, acne due to hyperandrogenization. A widely used antiacne drug, retinoic acid, can change the clinical presentation of CS and delay the diagnosis.MethodsWe report an atypical presentation of adrenocorticotropic hormone (ACTH)-dependent CS in a patient treated with retinoic acid due to severe acne.ResultsThree months after the discontinuation of retinoic acid treatment (at a dose of 40 mg daily for 6 months, with a 4 month break and then for an additional 6 months), a 17.5-year-old male presented with short stature (− 3.0 SD), muscle weakness, difficulty concentrating, insomnia, and depressed mood. Body weight (body mass index, 22 kg/m²), fat tissue distribution, pubertal status (testicular volume equal to 20 mL, pubarche V, axillarche present), and blood pressure were normal, and the patient’s bone age was equal to his chronologic age. His bone mineral density was decreased (Z-score, − 3.5 SD). The morning serum cortisol level was normal (8:00 am, 171.9 ng/mL) and did not decrease in the evening (8:00 pm, 178.9 ng/mL) or after 1 mg of dexamethasone (100.4 ng/mL). The patient’s urinary free cortisol was elevated on 3 occasions (274.5, 217.3, and 253.7 μg/day). Increased ACTH levels in the morning (97.5 to 141.1 pg/mL) and postcorticoliberine (577.6 pg/mL) pointed to ACTH-dependent CS. A magnetic resonance imaging scan of the pituitary gland confirmed the presence of a microadenoma.ConclusionRetinoic acid treatment may alter the clinical presentation of ACTH-dependent CS and consequently delay the diagnosis. (Endocr Pract. 2014;20:e119-e122)     

Congenital Craniopharyngioma and Hypercalcemia Induced by Parathyroid Hormone-Related Protein

ObjectiveTo report a case of congenital craniopharyngioma and parathyroid hormone-related protein (PTHrP)-associated humoral hypercalcemia.MethodsDetails of this unusual case are reviewed, from detection of fetal hydrocephalus and a brain tumor, through cesarean delivery at 36 weeks of gestation, to subsequent laboratory studies, management, and confirmation of the diagnosis.ResultsAlthough PTHrP has been well documented as a cause of humoral hypercalcemia of malignancy (HHM) in adult patients with cancer, HHM is uncommon in children. In addition, HHM has rarely been ascribed to nonmalignant tumors. To the best of our knowledge, we report the first case of a neonate with congenital craniopharyngioma and refractory hypercalcemia (peak ionized calcium level of 1.92 mmol/L; normal, 1.05 to 1.3) attributed to an elevated PTHrP value of 8.6 pmol/L (normal, less than 4.7). Intact parathyroid hormone was appropriately undetectable (less than 10 pg/mL; normal, 15 to 65). Despite calcitonin treatment, the hypercalcemia persisted. Although pamidronate infusion stabilized the serum calcium level, the baby did not survive.ConclusionThe diagnosis of craniopharyngioma was confirmed at autopsy, and immunohistochemical studies substantiated that the craniopharyngioma produced PTHrP. (Endocr Pract. 2007;13:67-71)     

Relationship of Adipokines and Proinflammatory Cytokines Among Asian Indians With Obesity and Youth Onset Type 2 Diabetes

Objective: It is well known that inflammation is associated with diabetes, but it is unclear whether obesity mediates this association in individuals with youth-onset type 2 diabetes mellitus (T2DM-Y).Methods: We recruited individuals with T2DM-Y (age at onset <25 years) and age-matched normal glucose tolerance (NGT) subjects. Participants were further classified using Asia-Pacific body mass index cut-points for obesity and categorized as: nonobese NGT (n = 100), Obese NGT (n = 50), nonobese T2DM-Y (n = 50), and obese T2DM-Y (n = 50). We compared adipokines (adiponectin and leptin) and proinflammatory cytokines (tumor necrosis factor alpha &lsqb;TNF-α] and monocyte chemotactic protein-1 &lsqb;MCP-1]) across groups.Results: Compared to nonobese NGT, the other 3 groups (obese NGT, nonobese T2DM-Y, and obese T2DM-Y) were found to have lower adiponectin (7.7 vs. 5.7, 4.2, 3.8 μg/mL, P<.01), and higher leptin (3.6 vs. 5.4, 5.7, 7.9 μg/mL, P<.001) and MCP 1 (186 vs. 272, 340, 473 pg/mL, P<.001) respectively. However, TNF-α levels were higher only among nonobese T2DM-Y (112 pg/mL) and obese T2DM-Y (141 pg/mL, P<.01 for each). After adjusting for age, sex, waist, hypertension, homeostatic model assessment of insulin resistance (HOMA-IR), serum cholesterol, triglycerides, and family history of diabetes, adiponectin was associated with 33% and 41% lower odds of being nonobese T2DM and obese T2DM, respectively. However, adjusted for same factors, leptin, TNF-α, and MCP-1 were associated with markedly higher odds (5- to 14-fold) of nonobese and obese T2DM.Conclusion: In young Asian Indians, leptin and proinflammatory cytokines are positively, and adiponectin negatively, associated with both nonobese and obese T2DM-Y compared to nonobese NGT individuals.Abbreviations: BMI = body mass index CI = confidence interval FPG = fasting plasma glucose HOMA-IR = homeostatic model assessment of insulin resistance IGT = impaired glucose tolerance MCP-1 = monocyte chemotactic protein-1 NGT = normal glucose tolerance OGTT = oral glucose tolerance test OR = odds ratio T2DM-Y = youth-onset type 2 diabetes TNF-α = tumor necrosis factor-α     

46,XX SRY-Positive Male Syndrome Presenting with Primary Hypogonadism in the Setting of Scleroderma

ObjectiveTo describe a case of SRY gene translocation in a man with scleroderma presenting with primary hypogonadism.MethodsWe present the clinical, physical, laboratory, and pathologic findings of the study patient and discuss the cytogenetic analysis and the cause of the sexual dysfunction. Relevant literature is reviewed.ResultsA 35-year-old man with a recent diagnosis of diffuse cutaneous sclerosis was referred by his rheumatologist because of a low testosterone level. His medical history was notable for right cryptorchidism corrected after birth. He had no history of sexual activity, but reported normal erectile function before his current presentation. Physical examination findings were remarkable for a height of 157.5 cm; weight of 72.7 kg; extensive, diffuse thickening of the skin; mild gynecomastia; little axillary and pubic hair; and soft testes (1-2 mL bilaterally). Initial laboratory testing revealed the following values: follicle-stimulating hormone, 22.1 mIU/mL (reference range, 1.4-18.1 mIU/mL); luteinizing hormone, 19.7 mIU/mL (reference range, 1.5-9.3 mIU/mL); total testosterone, 25 ng/dL (reference range, 241-827 ng/dL); and free direct testosterone, 0.8 pg/mL (reference range, 8.7-25.1 pg/mL). Laboratory test results were consistent with primary hypogonadism. A urologist performed testicular biopsy, which showed severe testicular atrophy with absent spermatogenesis. Primary hypogonadism due to Klinefelter syndrome or testicular fibrosis secondary to scleroderma was suspected. Karyotype analysis showed a 46,XX karyotype, and fluorescence in situ hybridization was consistent with a 46,XX,Xp22.3(SRY +) gene translocation. After a normal prostate-specific antigen level was documented, testosterone replacement therapy was initiated, and he was referred for genetic counseling.ConclusionsThe 46,XX SRY-positive male syndrome is rare. Adult diagnosis can be challenging because of normal sexual development. Scleroderma, which rarely can occur in Klinefelter-type syndromes, further complicated the diagnosis in this case. (Endocr Pract. 2011;17:95-98)     

Should Food Intake and Circadian Rhythm be Considered When Measuring Serum Calcitonin Level?

ObjectiveTo investigate the relationship between both food intake and circadian rhythmicity and serum calcitonin in the same individuals.MethodsEighteen healthy subjects, 10 males and 8females, aged 22 to 24 years, were recruited. Serum calcitonin level was measured three times: at 0800 after a 9-hour overnight fast, at 0900 postprandially, and at 1700 after another 9-hour fast. The same protocol was repeated once.ResultsThe mean calcitonin levels (at 0800) were 3.92 pg/mL (SD, 2.5 pg/mL) on Day 1 and 3.52 pg/mL (SD, 2.1 pg/mL) on Day 2. Mean postprandial calcitonin (at 0900) was 9.46 pg/mL (SD, 8.6 pg/mL) on Day 1 and 9.91 pg/mL (SD, 6.9 pg/mL) on Day 2. Mean fasting calcitonin in the evening (at 1700) was 6.74 pg/mL (SD, 4.73 pg/mL) on Day 1 and 6.49 pg/mL (SD, 3.57 pg/mL) on Day 2. There was no significant difference in the mean calcitonin level on days 1 and 2 for any of the three time points examined. Statistically significant differences were found between postprandial and evening calcitonin levels and the fasting levels on Day 1 (P = .018 and .015, respectively) and Day 2 (P = .001 and .0009, respectively).ConclusionThese results suggest that serum calcitonin level is significantly influenced by food intake in healthy young subjects and reveal a circadian rhythm, with increased calcitonin level during the afternoon. The timing of blood sampling relative to meals should be integrated into clinical practice and research settings involving serum calcitonin measurements. (Endocr Pract. 2013; 19:620-626)     

Recombinant Human Parathyroid Hormone Therapy (1-34) In an Adult Patient with a Gain-of-Function Mutation in the Calcium-Sensing Receptor-a Case Report

ObjectiveTo describe a case of hypocalcemia in a patient with a gain-of-function mutation in the calcium-sensing receptor that was undetected until adulthood and successfully treated with recombinant parathyroid hormone.MethodsThe clinical findings, laboratory data, and a review of the pertinent literature are presented.ResultsA 55-year-old woman was hospitalized and seen by the endocrinology consult service for hypocalcemia that was refractory to repeated doses of intravenous calcium gluconate. She expressed concern about chronic leg muscle cramps and paresthesias of the lips and fingertips. In addition, she had no history of neck surgery, neck irradiation, or any autoimmune disease. She was a well-appearing female with no dysmorphic features or skin changes. Laboratory tests revealed hypocalcemia, hyperphosphatemia, hypomagnesemia, and hypovitamino-sis D. Her parathyroid hormone concentration (PTH) was low at 14.2 pg/mL. Her PTH and calcium concentrations remained low despite repletion of magnesium and treatment with calcitriol and oral calcium replacement. A 24-hour collection for urinary calcium showed inappropriate hypercalciuria. Medical records showed her hypocalcemia to be chronic. Additionally, several family members had also complained of muscle cramps. A congenital cause of her hypoparathyroidism was considered, and genetic testing confirmed heterozygosity for a gain-of-function mutation in the calcium-sensing receptor gene associated with autosomal dominant familial isolated hypoparathyroidism (ADH). Treatment with subcutaneous recombinant human parathyroid hormone teriparatide (rhPTH [1-34]) 20 mcg twice daily for three days normalized her calcium and phosphorus concentrations.ConclusionrhPTH (1-34) is an effective treatment for patients with hypoparathyroidism due to gain-of-function mutations in the calcium-sensing receptor. ADH can be insidious in presentation and the diagnosis can be missed unless there is a high index of suspicion. (Endocr Pract. 2013;19:e24-e28)     

Virilizing Adrenal Ganglioneuroma in a Woman with Subclinical Cushing Syndrome

ObjectiveTo describe a patient with a virilizing adrenal ganglioneuroma and subclinical Cushing syndrome.MethodsDetailed clinical, laboratory, radiologic, and pathologic findings are presented, and the pertinent literature is reviewed.ResultsA 56-year-old postmenopausal woman was referred for evaluation of a 3.6- by 3.0-cm right adrenal mass, which had been diagnosed during a work-up for hirsutism. A bilateral oophorectomy done 2 months before the presentation failed to correct the elevated testosterone levels. On examination, she had severe hirsutism on her face, chest, back, and extremities, as well as male pattern baldness and clitoromegaly. Biochemical evaluation showed elevated total and free serum testosterone levels of 319 ng/dL (reference range, 20 to 70) and 78 pg/mL (reference range, 1 to 9), respectively, values in the adult male range. The serum dehydroepiandrosterone sulfate level was 117 μ/dL (reference range, 10 to 152), and the urine free cortisol was 10.4 μg/24 h (reference range, < 45). A laparoscopic adrenalectomy revealed a 5.0-cm adrenal ganglioneuroma containing nests of adrenocortical cells. On the first day postoperatively, the serum cortisol level was < 1.0 μg/dL. At 1 month after adrenalectomy, the total and free testosterone levels had declined to 16 ng/dL and 3.1 pg/mL, respectively. At 2 months postoperatively, normal results of a cosyntropin stimulation test (basal and peak cortisol levels of 13.6 and 20.0 μg/dL, respectively) indicated recovery of the hypothalamic-pituitary-adrenal axis.ConclusionTo our knowledge, this is the first case report of a virilizing adrenal ganglioneuroma with this unique pathologic finding and concomitant subclinical Cushing syndrome. (Endocr Pract. 2008;14:584-587)     

Endoscopic Ultrasound-Guided Fine-Needle Aspiration With Aspirate Assay to Diagnose Suspected Mediastinal Parathyroid Adenomas

ObjectiveTo describe our experience with mediastinal parathyroid adenomas diagnosed by endoscopic ultrasound-guided fine-needle aspiration (EUSFNA) and measurement of parathyroid hormone.MethodsWe describe the clinical and pathologic findings and diagnostic techniques used in 2 study patients.ResultsPatient 1 was a 54-year-old man with persistently elevated serum calcium and parathyroid hormone concentrations despite removal of a right inferior parathyroid adenoma. An echoendoscope was used to identify the lesion and to perform FNA. The parathyroid hormone concentration measured in the aspirated material was 1800 pg/mL. Pathologic examination of the resected specimen revealed a 29.7-g parathyroid adenoma. Patient 2 was an 86-year-old woman with recurrent hyperparathyroidism. A linear array echoendoscope was used to perform FNA of the lesion in her mediastinum. The parathyroid hormone concentration measured in the aspirated specimen was 6905 pg/mL.ConclusionsPreoperative localization of recurrent or persistent hyperparathyroidism is often difficult. EUSFNA allows evaluation of masses, such as those found in the mediastinum, that are poorly evaluated by other imaging modalities. This technique may be a useful adjunct in diagnosing mediastinal parathyroid adenomas. (Endocr Pract. 2010;16:437-440)     

Body mass index and the risk of rheumatoid arthritis: a systematic review and dose-response meta-analysis

IntroductionThe evidence from published studies on the association between obesity and rheumatoid arthritis has been contradictory. To clarify the association between obesity and rheumatoid arthritis, we conducted a systematic review and dose-response meta-analysis to assess the relationship between body mass index and rheumatoid arthritis risk.MethodsA systematic literature search of PubMed and Embase (up to 12 July 2014) was performed to identify all eligible published reports. The pooled relative risk results with corresponding 95% confidence intervals of rheumatoid arthritis development were estimated using a random-effects model.ResultsEleven eligible related citations fulfilled the inclusion criteria and were included in the study. Compared with individuals with a body mass index under 30, obese individuals showed an association with a significantly increased risk of rheumatoid arthritis (relative risk = 1.25, 95% confidence interval: 1.07 to 1.45, P_{heterogeneity} <0.01, I² = 63%). Compared to normal weight subjects, the pooled relative risks for rheumatoid arthritis were 1.31 (1.12 to 1.53) and 1.15 (1.03 to 1.29) for the categories of obese and overweight, respectively. In the dose-response analysis, there was evidence of a nonlinear association (P_nonlinear = 0.005) and the estimated summary relative risk for a 5-unit increment was 1.03 (95% confidence interval: 1.01 to 1.05, P_{heterogeneity} = 0.001, I² = 70.0%).ConclusionsAn increase in body mass index can contribute to a higher risk for rheumatoid arthritis development. However, the finding also highlights the need for research on the association between body mass index and rheumatoid arthritis risk with adjustment for more confounding factors.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0601-x) contains supplementary material, which is available to authorized users.     

Tibial Tenderness Identifies Secondary Hyperparathyroidism Responding to High-Dose Vitamin D in Pakistani Women

ObjectiveTo assess the utility of anterior tibial tenderness (ATT) measured by visual analogue scoring (VAS) as a clinical diagnostic tool for vitamin D deficiency in a high-risk population of Pakistani women.MethodsATT was measured by VAS in 75 premenopausal women age 17 to 56 years (mean, 41.3 years) with generalized aches and pains and calcium <11 mg/dL (normal, 8 to 11 mg/dL) who were seen at a tertiary care center in Lahore, Pakistan. This was followed by administration of 1.8 million units of vitamin D3 in divided doses. ATT, vitamin D, and parathyroid hormone (PTH) levels were checked before and after the injections. Correlation between ATT, vitamin D, and PTH, as well as changes in ATT, vitamin D, and PTH following supplementation were determined.ResultsPre-intervention average calcium and vitamin D were 9.3 mg/dL (range, 8 to 10.3 mg/dL) and 12.1 ng/mL (range, 1.5 to 32.6 ng/mL), respectively. Seventy-four percent of the participants (53/75) had vitamin D deficiency and elevated PTH (>60 pg/mL). Mean PTH was 81.6 pg/mL (range, 29.1 to 370 pg/mL). Changes in ATT correlated strongly (r = 0.422; P = .013) with changes in PTH. Following supplementation, there was significant improvement in ATT (P<.01) and vitamin D level (P<.01), with a decrease in PTH level (P<.01).ConclusionATT is a valid clinical diagnostic measure of vitamin D deficiency in South Asian women. (Endocr Pract. 2013;19:596-601)     

Cholecalciferol (Vitamin D3) Therapy and Vitamin D Insufficiency in Patients with Chronic Kidney Disease: A Randomized Controlled Pilot Study

ObjectiveTo investigate the efficacy of cholecalciferol (vitamin D3) in raising serum 25-hydroxyvitamin D (25[OH)]D) levels and reducing parathyroid hormone (PTH) levels in patients with chronic kidney disease (CKD).MethodsIn this double-blind, randomized controlled pilot study, participants with CKD stage 3 and 4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m²), vitamin D insufficiency (serum 25[OH]D < 30 ng/mL), and serum intact PTH levels > 70 pg/mL were randomly assigned to receive either 50 000 IU of cholecalciferol or placebo once weekly for 12 weeks. Primary outcomes (25[OH]D and PTH levels) were measured at baseline, week 6, and week 12. Secondary outcomes (1,25-dihydroxvitamin D and bone turnover markers) were measured at baseline and week 12. Because of skewed data distribution, statistical analyses were performed on a logarithmic scale. The difference between the group means was exponentiated to provide the geometric mean ratio. A linear mixed model using an unstructured variance-covariance matrix was used to examine change in the primary and secondary outcomes over time.ResultsGeometric mean serum 25(OH)D concentrations of the study groups were similar at baseline (P = .77). At week 6, a significant difference between the treatment and placebo groups was detected (P = .001); this difference was maintained at week 12 (P = .002). Among cholecalciferol- treated participants, serum 25(OH)D concentration increased on average from 17.3 ng/mL (95% confidence interval [CI], 11.8-25.2) at baseline to 49.4 ng/mL (95% CI, 33.9-72.0) at week 12. As-treated analysis indicated a trend toward lower PTH levels among cholecalciferol-treated participants (P = .07).ConclusionWeekly cholecalciferol supplementation appears to be an effective treatment to correct vitamin D status in patients with CKD. (Endocr Pract. 2008;14:10-17)     

Low Free (But Not Total) 25-Hydroxyvitamin D Levels in Subjects with Normocalcemic Hyperparathyroidism

Objective: Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by elevated parathyroid hormone (PTH) levels with persistently normal calcium levels. The diagnosis of NPHPT assumes the absence of secondary causes of elevated PTH levels. The objective of the current study was to examine levels of free 25-hydroxyvitamin D (25&lsqb;OH]D) in NPHPT subjects and healthy controls.Methods: Ten NPHPT subjects and 20 controls who were age, sex, race, and body mass index (BMI) matched were examined. The diagnosis of NPHPT was made if subjects had (1) a serum calcium level of 8.6 to 10.4 mg/dL, total 25(OH)D 30 to 40 ng/mL, and intact PTH (iPTH) ≥66 pg/mL; and (2) normal renal and liver function. Serum total 25(OH)D levels were measured by radioimmunoassay, and free 25(OH)D levels were determined using an enzyme-linked immunoassay.Results: Mean age of NPHPT subjects was 59.9 ± 5.4 years, and mean BMI was 28.4 ± 2.3 kg/m², which was not significantly different from the mean age and BMI of the control subjects. Mean total 25(OH)D level was 31.9 ± 1.7 ng/mL in NPHPT subjects and did not differ from that of the controls (32.7 ± 3.3 ng/mL; P = .52). However, mean free 25(OH)D was 5.0 ± 0.9 pg/mL in NPHPT subjects, which was 20% lower compared to the mean of the controls (6.2 ± 1.3 pg/mL; P = .013). Serum iPTH levels were inversely correlated with levels of measured free 25(OH)D (r = -0.42; P<.05) but did not correlate with levels of total 25(OH)D (r = -0.14; P>.10).Conclusion: Measured free 25(OH)D levels are lower in NPHPT subjects than in healthy control subjects. We suggest that some NPHPT subjects may actually have secondary hyperparathyroidism based on their free 25(OH) D levels.Abbreviations: 25(OH)D = 25-hydroxyvitamin D; BMI = body mass index; CV = coefficient of variation; DBP = vitamin D–binding protein; iPTH = intact parathyroid hormone; NPHPT = normocalcemic primary hyperparathyroidism