Silent Thyroiditis,Isolated Corticotropin Deficiency,and Alopecia Universalis in a Patient With Ulcerative Colitis and Elevated Levels of Plasma Factor VIII: An Unusual Case of Autoimmune Polyglandular Syndrome Type 3

ObjectiveTo describe an unusual case of autoimmune polyglandular syndrome (APS) type 3 and provide a brief review of the literature.MethodsWe present the clinical course and laboratory data of a patient with silent thyroiditis, isolated corticotropin (adrenocorticotropic hormone or ACTH) deficiency, alopecia universalis, and ulcerative colitis with an associated hypercoagulable state. The related literature is also reviewed briefly.ResultsA 43-year-old man who had a history of ulcerative colitis with an associated hypercoagulable state and alopecia universalis was referred to the endocrinology department for evaluation of fatigue and a mildly elevated level of thyrotropin (thyroid-stimulating hormone or TSH). He previously had mildly increased TSH levels, for which low-dose levothyroxine therapy had been prescribed. During use of this therapy, a suppressed TSH level developed, necessitating discontinuation of thyroid hormone therapy; a subsequent increase in TSH value was followed by a spontaneous return to euthyroidism. An ACTH stimulation test revealed adrenal insufficiency. His ACTH level was low, 21-hydroxylase antibodies were not present, and further testing demonstrated otherwise intact pituitary function. Magnetic resonance imaging of his pituitary gland showed normal findings. Treatment with hydrocortisone promptly decreased his fatigue. He was found to have an elevated factor VIII level as the cause of his hypercoagulable state. The patient continues to feel well with use of hydrocortisone therapy and has normal thyroid function.ConclusionThis patient’s components of APS type 3 have not been previously reported; thus, the complex nature of the APS variants is supported. (Endocr Pract. 2009;15:138-142)     

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)     

Transformation of a Pituitary Macroadenoma into to a Corticotropin-Secreting Carcinoma Over 16 Years

ObjectiveTo describe a case of a pituitary macroadenoma that differentiated into a corticotropin (ACTH)-secreting carcinoma with metastasis to the thigh.MethodsWe present a case report with a 16-year follow-up that includes anatomic and endocrine documentation of the history of an ACTH-secreting carcinoma.ResultsA 32-year-old woman presented for evaluation in 1989 because of visual feld defects. Magnetic resonance imaging revealed a locally invasive 3-cm macroadenoma. She had no clinical signs of cortisol excess. The patient underwent surgical debulking followed by a course of radiation directed to the pituitary. Results from retrospective immunohistochemical staining with antibodies against ACTH, prolactin, and MIB-1 were negative. Postoperatively, she could not be weaned from exogenous steroids without developing symptoms of adrenal insuffciency. In 1995, she developed left facial palsy and diplopia caused by tumor growth. In 1997, the patient developed progressive symptoms of cortisol excess, which continued after exogenous steroid replacement was discontinued. The patient’s clinical status continued to deteriorate because of local mass effect from tumor growth and uncontrolled hypercortisolism. She underwent bilateral adrenalectomy in 2003. The patient remained debilitated in a long-term care facility for 2 years when she was found to have a mass on her left hip. Biopsy results of the obturator muscle revealed metastatic tumor of neuroendocrine origin with strong reactivity to ACTH antibodies and MIB-1 labeling in 8% of tumor cell nuclei.ConclusionA pituitary tumor can transform into an ACTH-secreting carcinoma in an indolent manner. Patients with invasive pituitary adenomas require long-term surveillance to monitor for differentiation into pituitary carcinoma. (Endocr Pract. 2007;13:463-471)     

Changes in Steroid Concentrations with the Timing of Corticotropin Stimulation Testing in Participants with Adrenal Sufficiency

ObjectiveTo determine whether the time of day at which corticotropin stimulation testing is performed influences the steroid concentrations observed in persons with normal adrenal function.MethodsIn this retrospective, secondary analysis, participants with normal adrenal function were studied to determine whether the time of corticotropin stimulation testing influenced results. Participants consisted of 2 groups: healthy volunteers who were not suspected of having adrenal insufficiency and patients being tested for adrenal insufficiency as part of their standard of care who were subsequently shown to have normal adrenal function on the basis of a peak cortisol value of at least 20 μg/dL. A high-dose corticotropin stimulation test was performed in all participants. Baseline, peak, and delta steroid concentrations were documented after corticotropin injection. Steroid concentrations were measured by tandem mass spectrometry. Multivariate analyses adjusted for patient age, sex, and baseline steroid concentrations.ResultsWith progression through the day for the time of testing, the baseline cortisol concentration decreased, while the peak and delta cortisol concentration increased (P values: < .001, .007, .007, respectively). For 11-deoxycortisol, the baseline decreased, while peak and delta values increased with later testing (P values: .017, .012, .02, respectively). Peak aldosterone concentrations increased according to their baseline values (P < .001), but were unaffected by time. Peak and delta dehydroepiandrosterone concentrations increased with time (P = .015 and .021, respectively). Referring to the various criteria for adequate steroid responses to corticotropin available in the literature, the time-related differences in this small group of patients were insufficient to draw different conclusions about results of testing.ConclusionsCortisol, 11-deoxycortisol, and dehydroepiandrosterone values were most influenced by testing times. In patients with borderline adrenal function who are tested at different times of the day, the modest differences we observed may be sufficient to affect conclusions about whether adrenal insufficiency is present. (Endocr Pract. 2012;18:66-75)     

Long-Term Management with Octreotide or Cabergoline in Ectopic Corticotropin Hypersecretion: Case Report and Literature Review

ObjectiveTo describe the corticotropin response to long-term octreotide or cabergoline administration in a patient with ectopic corticotropin secretion who underwent adrenalectomy.MethodsWe describe the clinical, radiologic, and biochemical findings of the study patient over the course of 18 years.ResultsA 40-year-old woman was evaluated for Cushing syndrome. On the basis of biochemical indices, Cushing disease was diagnosed and pituitary exploration was performed. No cure was achieved. Computed tomography of the chest revealed a right lung nodule due to a lung carcinoid tumor that was then surgically excised. Because of persistent hypercortisolism, total adrenalectomy was performed. Subsequently, corticotropin levels rose dramatically and hyperpigmentation developed while serum cortisol was in the reference range. The patient was treated with octreotide for 3 years and then with cabergoline for 8 years. While taking octreotide, corticotropin values decreased, accompanied by depigmentation and development of signs of adrenal insufficiency, which led to the reinstitution of supplemental hydrocortisone. Cabergoline induced a similar long-lasting effect on the clinical and biochemical parameters observed. Eight years later, she is still treated with cabergoline, and no lung tumor has been detected.ConclusionsIn this patient with ectopic Cushing syndrome, treatment with either octreotide or cabergoline markedly reduced corticotropin levels and hyperpigmentation. (Endocr Pract. 2010;16:829-834)     

Hypocortisolemia in Graves Hyperthyroidism

ObjectiveTo assess the risk of concomitant adrenal sufficiency in 2 patients with Graves thyrotoxicosis.MethodsWe present the clinical course and laboratory findings of 2 patients with hyperthyroidism associated with low basal serum cortisol and briefly review the literature with regard to possible mechanisms of hypocortisolemia in thyrotoxic states.ResultsTwo women aged 37 and 43 years with longstanding Graves disease presented with hyperthyroidism secondary to nonadherence to prescribed antithyroid medications. Both women also had symptoms suggestive of adrenal insufficiency including nausea, vomiting, and diffuse abdominal pain in Patient 1 and fatigue and hypotension in Patient 2. In both patients, physical examination findings were consistent with hyperthyroidism. Laboratory results of Patient 1 included the following: thyrotropin, < 0.002 mIU/L; free thyroxine, > 6 μg/dL; and total triiodothyronine, 539 ng/dL. Laboratory results of Patient 2 included the following: thyrotropin, < 0.002 mIU/L; free thyroxine, > 6 μg/dL; and total triiodothyronine, 539 ng/dL. Morning basal cortisol levels were 0.9 μg/dL in Patient 1 and 0.6 pg/dL in Patient 2. Because of the low basal serum cortisol levels, the patients underwent a high-dose (250 mcg) cosyntropin-stimulation test; however, both patients had adequate cortisol response. At 60 minutes, serum cortisol concentration was 31.4 μg/dL in Patient 1 and 25.5 pg/dL in Patient 2. After adequately treating the hyperthyroidism, basal cortisol levels in both patients returned to the reference range.ConclusionSymptomatic hypocortisolemia may be present in severe hyperthyroidism, and it resolves with adequate treatment of the hyperthyroidism. (Endocr Pract. 2009;15:220-224)     

Isolated ACTH deficiency associated with transient thyrotoxicosis and hyperprolactinemia

A 43-year-old woman with isolated ACTH deficiency in association with transient thyrotoxicosis is reported. The initial evaluation revealed that plasma ACTH and cortisol did not respond to corticotropin-releasing hormone (CRH) in the presence of hyperthyroxinemia and hyperprolactinemia. During the replacement therapy with dexamethasone, she developed transient hypothyroxinemia with persistent hyperprolactinemia. Although thyroid open biopsy did not show any evidence of autoimmune thyroiditis or subacute thyroiditis, the data appear to provide other evidence of a possible relationship between acute adrenal insufficiency and transient thyroid dysfunction.     

Latent Adrenal Insufficiency: Concept,Clues to Detection,and Diagnosis

In 1855, Thomas Addison described an illness now known as Addison disease (AD) caused by damage to the adrenal cortex and manifesting in weakness, weight loss, hypotension, gastrointestinal disturbances, and brownish pigmentation of the skin and mucous membranes. Corticosteroid supplementation, corticotropin (adrenocorticotropic hormone [ACTH] of medicinal use) test, and anti-adrenal auto-antibodies (AA) have come into use in the 100 years since Addison's death. Following the methodological innovations, 4 disorders which share impaired response to corticotropin in common have been discovered (i.e., partial AD, apigmented adrenal insufficiency [AI], subclinical AI, and the AA-positive state exclusively in subjects proven to have an impaired response to corticotropin). As they are hidden, potentially serious conditions, these disorders are bound together as latent AI (LAI). Diagnosis of AD is often delayed, which may lead to adrenal crisis. If LAI were widely recognized, such delays would not exist and crises would be averted. The 3 existing guidelines do not refer much to LAI patients outside those in acute situations. To address this, information relevant to clinical manifestations and diagnostic tests of LAI was sought in the literature. Signs and symptoms that are useful clues to begin a diagnostic workup are presented for endocrinologists to identify patients with suspected LAI. The utility of 2 corticotropin test protocols is reviewed. To endorse LAI shown by the corticotropin test, monitoring items following corticosteroid supplementation are cited from the guidelines and supplemented with the author's observations.Abbreviations: AA = anti-adrenal auto-antibodies; Ab = antibodies; ACA = AA detected by immunofluorescence; ACTH = adrenocorticotropic hormone; AD = Addison disease; AI = adrenal insufficiency; DHEA = dehydroepiandrosterone; GC = glucocorticoid; IFA = immunofluorescence assay; LAI = latent AI; LDT = low-dose test; MC = mineralocorticoid; 21OHAb = anti-21-hydroxylase Ab; ST = standard test; URI = upper respiratory infection     

Glucocorticoid- and Androgen-Secreting Black Adrenocortical Adenomas: Unique Cause of Corticotropin-Independent Cushing Syndrome

ObjectiveTo describe the unique association of corticotropin-independent Cushing syndrome caused by cortisoland androgen-secreting black adrenal cortical adenomas with myelolipomatous change.MethodsWe report the clinical, laboratory, radiologic, and pathologic findings from 2 patients who presented with androgen excess and typical signs and symptoms of Cushing syndrome.ResultsEndocrine investigations showed high serum cortisol concentrations that lacked diurnal rhythm, undetectable plasma corticotropin concentrations, and absence of serum cortisol suppression after overnight dexamethasone suppression tests. Serum levels of adrenal androgens were elevated. Computed tomography of the abdomen revealed unilateral adrenal masses (largest lesional diameters 4.0 and 3.1 cm). On the basis of the plurihormonal hypersecretion and the imaging characteristics, adrenocortical carcinoma was considered as a possible diagnosis. However, histopathologic analysis in both patients revealed black adrenal cortical adenomas with myelolipomatous change. After surgery, adrenal androgens normalized, and the signs and symptoms of Cushing syndrome and androgen excess resolved. There was no evidence of recurrent disease at last follow-up.ConclusionsA unique form of corticotropin-independent Cushing syndrome is described: cortisoland androgen-secreting black adrenal cortical adenomas with myelolipomatous change. Although most patients with corticotropin-independent Cushing syndrome associated with androgen excess prove to have adrenocortical carcinoma, the clinician should be aware of the possibility of benign, black adrenal adenomas in this clinical setting. (Endocr Pract. 2011;17:e73-e78)     

Thyrotoxicosis due to Ectopic Lateral Thyroid Tissue Presenting 5 Years After Total Thyroidectomy

ObjectiveTo describe a patient who, 5 years after total thyroidectomy to treat Graves disease, presented with thyrotoxicosis due to nonmalignant lateral ectopic thyroid tissue.MethodWe describe the laboratory, imaging, and physical findings of the study patient and review the relevant literature.ResultsA 32-year-old white woman with a history of Graves disease presented with recurrent hyperthyroidism 5 years after total thyroidectomy. A radioactive iodine scan was performed, which revealed elevated uptake (40%) and positive imaging in the left mid-neck. Ultrasonography examination of the neck confirmed the absence of any thyroid tissue within the thyroid bed, but documented 2 nodular, hypoechoic left upper-neck masses with punctuate hyperlucency. Contrast-enhanced computed tomography was performed to precisely localize the nodules, which were excised surgically via selective neck dissection. Histopathologic examination revealed chronic lymphocytic inflammatory infiltrate with focal thyroid hyperplasia and papillary infoldings and no evidence of malignancy.ConclusionsTo our knowledge, this represents the first report of ectopic benign thyroid tissue as the sole cause of hyperthyroid symptoms, and this entity should be considered in patients who have undergone thyroidectomy and have persistent hyperthyroidism. (Endocr Pract. 2011;17:70-73)     

Paradoxical surge of corticotropin after glucocorticoid replacement in central adrenal insufficiency

A 78-yr-old man was admitted in emergency with fatigue, anorexia, vomiting, hypothermia (35.1 °C on a hot August day), hypotension (89/56 mmHg) and hyponatraemia (126 mEq/l). Plasma corticotropin and cortisol were severely depressed: 0.84 pmol/L and 33.1 nmol/L respectively (reference range, 1.5-13.9 pmol/L and 110-505 nmol/L, respectively). Thyroid stimulating hormone was low-normal and free-triiodothyronine and free-thyroxine were subnormal. Magnetic resonance imaging revealed swelling of the pituitary gland and the stalk. The patient recovered after glucocorticoid replacement (200 mg/day intravenous hydrocortisone on Day 1 followed by tapering). Central diabetes insipidus which had become apparent had been treated with 1-desamino-8-D-arginine vasopressin. A surge of corticotropin and cortisol, 19.4 pmol/L and 712.1 nmol/L respectively, was found on Day 5 when luteinizing hormone, follicle stimulating hormone, and testosterone were subnormal and prolactin was slightly elevated. Subsequently, corticotropin and cortisol levels normalized together with normalization of luteinizing hormone, follicle stimulating hormone, anti-diuretic hormone, thyroid stimulating hormone, prolactin, testosterone and thyroid hormone levels. Shrinkage of the pituitary gland occurred after one month. Serum immunoglobulin G4 was elevated (3.21 and 6.02 g/l at 1- and 3-month follow-ups respectively). In conclusion, a paradoxical surge of corticotropin after glucocorticoid replacement was observed in a patient with central adrenal insufficiency due to immunoglobulin G4-related hypophysitis. Surge of ACTH in central adrenal insufficiency after glucocorticoid replacement has rarely been reported, and this is the second such case report.     

The Low-Dose Acth Stimulation Test: is 30 Minutes Long Enough?

Objective: Controversy persists regarding the use of the low-dose adrenocorticotropic hormone (ACTH) stimulation test (LDST) for the diagnosis of adrenal insufficiency (AI) and optimal test result interpretation. However, many centers are now using the LDST to assess cortisol secretion adequacy, and some only use a 30-minute cortisol level to determine adrenal sufficiency or AI. This study examined both 30- and 60-minute cortisol levels to assess whether the interpretation of the test was affected when both cortisol levels were taken into consideration.Methods: Data were obtained by retrospective chart review from a single pediatric endocrinology unit over a 7-year period. We identified 82 patients who completed the LDST. Their mean age was 11.7 years, and 37% were female. Cortisol levels were evaluated at baseline and 30 and 60 minutes after cosyntropin administration. A cutoff value ≥18 μg/dL was used to define adrenal sufficiency.Results: We found that 54% of patients reached peak cortisol levels at 60 minutes, and 11 patients who did not pass the test at 30 minutes did so at 60 minutes. The only predictive characteristic was weight status; overweight and obese individuals tended to peak at 30 minutes, and normal and underweight individuals tended to peak at 60 minutes.Conclusion: Although further studies are necessary to confirm our findings, it appears that measuring cortisol both 30 and 60 minutes following synthetic ACTH administration may be necessary to avoid overdiagnosing AI.Abbreviations: ACTH = adrenocorticotropic hormone AI = adrenal insufficiency BMI = body mass index LDST = low-dose ACTH stimulation test MRI = magnetic resonance imaging     

Unusual Clinical Course of Graves’ Thyrotoxicosis and Concomitant Sarcoidosis: Case Report and Review of Literature

ObjectiveTo report a case of Graves’ disease with concomitant sarcoidosis involving the thyroid gland.MethodsWe present the clinical, laboratory, imaging, and pathologic findings and describe the clinical course of a patient with Graves’ disease and sarcoidosis, who was unresponsive to propylthiouracil and radioiodine treatment.ResultsA 23-year-old woman presented with thyrotoxicosis and a large goiter. Laboratory studies and findings on thyroid uptake and scan were consistent with Graves’ disease. She was also found to have hilar lymph-adenopathy and hepatosplenomegaly. Despite treatment with antithyroid drugs and radioiodine therapy, her hyperthyroidism persisted. Surgical resection of the thyroid gland and 2 lymph nodes disclosed noncaseating granulomas, consistent with sarcoid.ConclusionAutoimmune endocrinopathies and, less commonly, thyroid autoimmune disease have been reported in patients with sarcoidosis. Similarities exist in the pathogenesis of these two conditions. Concomitant sarcoidosis in the thyroid gland in patients with Graves’ disease may contribute to the resistance to antithyroid drugs and radioiodine therapy. (Endocr Pract. 2007;13:159-163)     

Hyperthyroidism due to Coexistence of Graves’ Disease and Struma Ovarii

ObjectiveTo report an unusual case of persistent thyrotoxicosis after treatment of Graves’ disease, because of coexistence of struma ovarii.MethodsWe report the clinical history, imaging studies, laboratory and pathologic data, and treatment in a patient with persistent hyperthyroidism after surgical treatment of Graves’ disease. In addition, we discuss some aspects of the pathogenesis of hyperthyroidism due to functioning struma ovarii.ResultsA 42-year-old woman underwent near-total thyroidectomy for treatment of Graves’ disease. Post-operatively, hyperthyroidism was still present. Methimazole was administered again, and performance of a ¹³¹I whole-body scan demonstrated a focus of intense uptake in the pelvis. Pelvic ultrasonography revealed a mass (11 by 8 by 7.1 cm) arising from the right ovary, with both solid and cystic components. Abdominal surgical exploration was performed, and the final histologic diagnosis was struma ovarii. The symptoms of hyperthyroidism diminished, and 3 weeks postoperatively, the thyroid hormone levels were in the hypothyroid range.ConclusionIn patients with refractory hyperthyroidism after thyroid surgical treatment, radioiodine scanning should be performed to diagnose or exclude the functioning profile of ovarian masses. (Endocr Pract. 2007;13:274-276)     

Cushing Syndrome in a Young Woman Due to Primary Pigmented Nodular Adrenal Disease

ObjectiveTo report a case of Cushing syndrome due to apparently sporadic primary pigmented nodular adrenal disease in a young woman.MethodsWe describe the clinical, biochemical, radiologic, and histologic findings of Cushing syndrome due to the rare condition of primary pigmented nodular adrenal disease.ResultsA 30-year-old woman presented with a 2-year history of worsening itch without rash over her shoulders and arms and weight gain, particularly around the abdomen and face. Careful questioning did not elicit any history of exogenous glucocorticoid use (systemic or topical), including hydrocortisone. On examination, the patient had a slightly rounded and plethoric face, a small buffalo hump, central adiposity, and thin skin with a few small striae on her inner thighs. No features of the Carney complex were observed. Investigations showed hypercor- tisolism with suppressed corticotropin and normal adrenal imaging despite documentation of enlarged adrenal glands at removal. High-dose dexamethasone administration was followed by a decrease in urinary free cortisol excretion rather than a paradoxical rise as previously reported in primary pigmented nodular adrenal disease. No mutations were detected in the PRKAR1A gene.ConclusionsPrimary pigmented nodular adrenal disease should be suspected in patients with corticotropinindependent Cushing syndrome who have normal adrenal imaging. The role of genetic testing in apparently sporadic cases is not established, but cumulative experience may be helpful in defining the frequency of PRKAR1A mutations. (Endocr Pract. 2010;16:84-88)     

Systemic Effects of Fluticasone Nasal Spray: Report of 2 Cases

ObjectiveTo describe two clinical cases of systemic side effects from use of fluticasone nasal spray.MethodsA retrospective review of medical records of two patients using this drug was undertaken, and their clinical presentations and laboratory data are summarized.ResultsDespite many clinical reports about the potential side effects from inhaled corticosteroids, no previously published clinical reports or studies have addressed such problems with the use of potent glucocorticoid nasal sprays. Two patients are described in whom different clinical problems developed after overuse of fluticasone nasal spray, a commonly advertised and prescribed drug. One patient was admitted to the hospital with symptoms of adrenal insufficiency. In the other patient, bone mineral density decreased substantially in 1 to 2 years despite preventive estrogen therapy. These patients had suppressed plasma or urinary cortisol, a low plasma adrenocorticotropic hormone (corticotropin) level, or an abnormal response to a cosyntropin stimulation test.ConclusionPatients should be clearly warned that the prescribed dosing for fluticasone nasal spray should be carefully followed because overuse may cause serious side effects. (Endocr Pract. 2005;11:194-196)     

Cushing’s Disease and Pregnancy: Case Report and Literature Review

ObjectiveTo describe a patient with untreated Cushing’s disease who had 2 spontaneous pregnancies that resulted in healthy babies on both occasions.MethodsWe present a case report with clinical, laboratory, and imaging data and discuss the literature pertaining to pregnancy in patients with Cushing’s syndrome.ResultsA 28-year-old woman came to our endocrinology clinic with a 1-year history of symptoms and signs of Cushing’s syndrome. An elevated 24-hour urinary cortisol excretion and an unsuppressed 1-mg overnight dexamethasone test confirmed the diagnosis. On her next visit, she reported a confirmed pregnancy, which ultimately resulted in the birth of a normal child. Further work-up subsequently showed 2 elevated 24-hour urinary cortisol values, loss of diurnal variation, and an elevated corticotropin level. There was lack of suppression on low-dose and high-dose overnight dexamethasone suppression tests. Magnetic resonance imaging of the pituitary showed normal findings. Inferior petrosal sinus sampling was recommended, but she declined the procedure. The patient returned 3 years later for reevaluation, at which time she reported the birth of another healthy child by cesarean delivery 10 months previously. There were no reported maternal or fetal complications. Examination at this visit revealed buccal pigmentation and proximal myopathy. Investigations showed increased 24-hour urinary cortisol excretion and serum corticotropin levels. Repeated magnetic resonance imaging disclosed a microadenoma on the right side of the pituitary. Unstimulated inferior petrosal sinus sampling showed a gradient to the right; thus, the presence of pituitary-dependent Cushing’s disease was confirmed.ConclusionOur case demonstrates that patients with pituitary-dependent Cushing’s disease are more likely to have spontaneous pregnancies with favorable outcomes than are patients with Cushing’s syndrome due to other causes. Our patient, despite having Cushing’s disease for more than 7 years, had 2 uneventful pregnancies that produced normal healthy children, without exacerbation of her disease during pregnancy. (Endocr Pract. 2007;13: 296-299)     

Association of ipilimumab therapy for advanced melanoma with secondary adrenal insufficiency: a case series

ObjectiveTo present a case series of ipilimumabrelated secondary adrenal insufficiency.MethodsIn this cases series, we review the presentation, evaluation, diagnosis, and management of patients with advanced melanoma who received ipilimumab and were referred to our endocrinology clinic for evaluation of hormonal abnormalities.ResultsSeven patients presented with symptoms, signs, or biochemical evidence of adrenal insufficiency 6 to 12 weeks after starting ipilimumab therapy. Ipilimumab is a cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibody that is approved for the treatment of metastatic melanoma and has widespread use for this disease. All 7 patients had biochemical evidence of profound secondary adrenal insufficiency. Thyroid function abnormalities, central hypogonadism, and low insulinlike growth factor 1 levels were seen in a subset of patients. Only 2 patients had abnormal findings on pituitary magnetic resonance imaging. Posterior pituitary function remained normal.ConclusionsOur findings suggest that the enhanced immune response associated with ipilimumab therapy may have a predilection for corticotroph and possibly thyrotroph cells. We recommend periodic hypothalamic-pituitary-adrenal axis monitoring for patients on this therapy.(Endocr Pract. 2012;18:351-355)     

Overt and Subclinical Adrenal Insufficiency in Pulmonary Tuberculosis

BackgroundTuberculosis of the adrenal glands may cause overt or subclinical adrenal insufficiency. An algorithm-based approach including assessment of paired basal cortisol and plasma adrenocorticotropic hormone (ACTH), short Synacthen, and plasma renin activity assays could be useful to diagnose all forms of adrenal insufficiency.MethodsThis cross-sectional study included consecutive, treatment-naive subjects diagnosed with pulmonary tuberculosis. Tuberculosis severity was classified by radiological criteria. Baseline parameters plus morning (8 am) serum cortisol and paired plasma ACTH were measured in all patients. Synacthen stimulation tests and plasma renin activity assays were performed as required.ResultsEighty-four treatment-naive consecutive cases of pulmonary tuberculosis were evaluated for adrenal insufficiency. Twenty-seven (32.14%) subjects had normal adrenocortical function and 8 (9.5%), 7 (8.3%), 40 (47.6%), and 2 (2.4%) subjects had stage 1, stage 2, stage 3, and stage 4 adrenal insufficiency, respectively. Serum cortisol was negatively correlated with radiological severity (P = .01) and duration of illness (P = .001). Adrenal dysfunction was present in 27.3%, 82.5%, and 80% of those with radiologically minimal, moderately advanced, and far-advanced disease, respectively. Mean cortisol was 19.74 ± 5.52, 17.42 ± 8.53, and 15.71 ± 7.14 (μg/dL) in the 3 groups, respectively (P = .042). Hyponatremia was present in 83.3% of the patients. Serum sodium was negatively correlated with severity but not with the duration of disease.ConclusionThe prevalence of overt and subclinical adrenal dysfunction in pulmonary tuberculosis was high and was correlated with disease severity and duration. An algorithmic approach may be useful to detect the same and may have important clinical implications.     

Anticuerpos antihipófisis en pacientes con sospecha de hipofisitis autoimmune

IntroductionDefinitive diagnosis of autoimmune hypophysitis (AH) is histological. However, a presumptive diagnosis can be made through clinical, biochemical and imaging data.ObjectiveThe objective of this study was to review the presence of antipituitary antibodies (APA) and antithyroid antibodies (ATA) in patients with suspected AH in order to determinate the utility of APA in the diagnosis of AH.Material and methodsWe studied 36 patients divided into seven groups according to the data suggesting AH (isolated corticotropin deficiency, other idiopathic pituitary deficiencies, idiopathic hyperprolactinemia, empty sella, sellar mass with thickened stalk, proven histological hypophysitis) or because of previous autoimmune endocrine diseases. Twenty-four controls without endocrinological disease were also included. In all subjects, APA were determined by immunofluorescence over primate pituitary gland and ATA by an agglutination technique.ResultsNone of the controls and only 9 patients, all of them women, were APA-positive. Of the 9 APA-positive patients, 43% belonged to the group of patients with isolated ACTH deficiency. In 8 patients, APA were determined again during the follow-up; 6 remained APA-negative, but one patient became APA-positive and another became APA-negative. ATA were positive in 12 patients, 22.2% of whom were also APA-positive, and in one control.ConclusionsThe prevalence of APA positivity among the study patients was low. These antibodies were found only in women, mostly with isolated corticotropin deficiency. APA and ATA coexisted in only 22% of the patients studied.