Stature after 18 months of treatment with synthetic growth hormone in 12 patients with Turner's syndrome

The increased availability of recombined human growth hormone (rhGH) allows its possible use in clinical situations not classically recognized as regular indications. Among these, the Turner's short stature is presently under experimental evaluation for its responsiveness to rhGH. Twelve patients, 10 with a 45, X karyotype, 1 46 XXiq, and 1 mosaicism, have been given rhGH at a dosage of 0.15 U/kg per injection six times a week. Mean age at onset of treatment was 12.8, mean growth retardation was 4.1 SDS according to Sempé. After 18 months of treatment mean growth catch-up was 0.9 SDS. Maximal velocity was reach during the first trimester of treatment and decreased thereafter but was above normal for bone age in all but 2 after 18 months. The bone age increased less than structural age. No side effects were reported. At the present time the efficacy of rhGH in increasing final height in Turner's patients is likely but not demonstrated by any studies. The exact place of ovarian substitution, even during the prepubertal period, is still matter of discussion. Since the velocity response to rhGH was maximal among the youngest patients an early diagnosis of the syndrome will likely be necessary to improve final stature.     

Suppressibility of Parathyroid Hormone in Primary Hyperparathyroidism

ObjectiveTo describe an unusual case of pathologically confirmed primary hyperparathyroidism in a patient presenting with severe hypercalcemia and an undetectable parathyroid hormone (PTH) level.MethodsWe present a detailed case report and outline the serial laboratory findings. In addition, the possible causes of low serum PTH levels in the setting of primary hyperparathyroidism are discussed.ResultsA 16-year-old female patient presented with severe epigastric pain, found to be attributable to acute pancreatitis. At hospital admission, her serum calcium concentration was high (14.0 mg/dL); the patient also had a normal serum phosphorus level of 3.6 mg/dL and an undetectable PTH level (< 0.2 pmol/L). An evaluation for non-PTH-mediated causes of hypercalcemia revealed a partially suppressed thyroid-stimulating hormone concentration and a below normal 1,25-dihydroxyvitamin D level, consistent with her suppressed PTH. One week after the patient was dismissed from the hospital, repeated laboratory studies showed a serum calcium value of 11.1 mg/dL, a serum phosphorus level of 2.8 mg/dL, and an elevated PTH concentration of 11.0 pmol/L, consistent with primary hyperparathyroidism. A repeated 1,25-dihy-droxyvitamin D measurement was elevated. A parathyroid scan showed a parathyroid adenoma in the left lower neck area, and she subsequently underwent successful surgical resection of a pathologically confirmed parathyroid adenoma.ConclusionThis case demonstrates that the serum PTH level can be suppressed in patients with primary hyperparathyroidism. Moreover, it emphasizes the need for careful evaluation of the clinical context in which the PTH measurement is determined. Consideration should be given to repeating measurement of PTH and serum calcium levels when the initial laboratory evaluation of hypercalcemia is unclear because dynamic changes in calcium metabolism may occur in the presence of secondary contributing factors. (Endocr Pract. 2007;13:785-789)     

Long term follow up of untreated primary hyperparathyroidism.

Fourteen patients with primary hyperparathyroidism and whose initial serum calcium concentrations were 2.75 mmol/l (11.0 mg/100 ml) or more were followed up for five to 23 years without operative treatment. One had osteitis fibrosa when seen and died with a fibrosarcoma 22 years later. The remaining 13 patients, who were followed up for a mean of 10 years, came to little obvious harm from not being operated on. Their serum calcium concentrations did not rise and there was no evidence of progressive renal impairment. In four patients who presented originally with renal calculi there were three further episodes of renal colic in 54 patient years of follow up. Conservative management of primary hyperparathyroidism is not an unreasonable option, and patients who do not have symptoms need not necessarily be pressed to accept surgery.     

Hyperparathyroidism associated with Cushing's syndrome due to an adrenal cortical adenoma

Two patients with the rare association of Cushing's syndrome and primary hyperparathyroidism are reported. Initially, both patients suffered from Cushing's syndrome due to adrenal cortical adenomas with typical features and laboratory findings. Five years after treatment of the Cushing's syndrome by removal of the tumor, asymptomatic mild hypercalcemia was incidentally noticed in both patients, which suggested the occurrence of primary hyperparathyroidism. An enlarged parathyroid gland was removed surgically in both cases and was histologically shown to be a parathyroid adenoma. The levels of serum calcium returned to normal after parathyroidectomy. Papillary adenocarcinoma of the thyroid in one patient and adenomatous goiter in the other were also incidentally detected at operation. These findings suggest that Cushing's syndrome resulting from an adrenal cortical adenoma may be another presentation of multiple endocrine neoplasia type I.     

Oral Calcium-loading Test in Infancy,with Particular Reference to Idiopathic Hypercalcaemia

An oral calcium-loading test suitable for infants is described and the usual response defined. In four acute cases of idiopathic hypercalcaemia a high and sustained rise in serum calcium occurred, suggestive of hyperabsorption and consistent with a vitamin-D-like effect. In four further infants with a milder illness suggestive of hypercalcaemia the fasting calcium levels were not grossly raised, but the test produced an exaggerated hypercalcaemic response. In this type of patient the test is more sensitive in the diagnosis of idiopathic hypercalcaemia than isolated measurements of serum calcium, especially if these are taken in the fasting state. Five patients on treatment and three whose treatment had been discontinued (but who subsequently relapsed or made a poor recovery) showed abnormal loading tests at a time when fasting calcium levels were normal. In two cases full recovery from the disease was associated with reversion of the test to normal. The test can therefore be used to indicate activity of the disease and consequently as a guide to therapy. In two cases a persistently abnormal loading test was associated with a poor long-term prognosis.     

Growth hormone reserve capacity in Turner's syndrome.

In 11 untreated and 6 oestrogen-treated Turner's syndrome patients, the changes in the serum growth hormone level were studied following the induction of hypoglycaemia with insulin. The growth hormone was measured with a radioimmune assay technique. The growth hormone peak value measured in healthy females was 54.32 +/- 17.17, in untreated Turner's syndrome was 14.90 +/- 3.71, and in oestrogen-treated Turner patients was 33.38 +/- 9.22 microU/ml (average +/- standard error). On the basis of the results, a role is attributed to the decreased growth hormone reserve in the low growth of Tuner's syndrome patients.     

Isochromosome Yq in a woman with atypical Turner's syndrome

Summary A female with 46,X,i(Ya) in all cells and a survey of previous cases of isochromosome Yq is presented.She was first admitted to hospital 15 years old due to nanismus and retarded sexual development. Gonadal dysgenesia was observed, and the diagnosis atypical Turner's syndrome was applied.The patient, who presents only a few Turner stigmata, has been given cyclic estrogen treatment since the age of 16. She has developed normal secondary sex characteristics, cyclic bleedings and has attained normal height (161 cm). Since the age of 18 the patient has suffered various periods of anemia caused by gastrointestinal hemorrhage. This hemorrhage is probably due to intestinal teleangiectasiae which are found with increased frequency in patients with Turner's syndrome.     

Partial long arm deletion of one X chromosome in a patient with secondary amenorrhea

Summary A partial long arm deletion of one X chromosome was observed in a patient with secondary amenorrhea and with no features of Turner's syndrome. It was shown that the deleted X chromosome was the inactivated one in all metaphases of the lymphocyte culture and of the tissue culture from gonadal biopsy.The patient was detected during a cytogenetic study of secondary amenorrhea of ovarian origin.     

G-11 staining in Turner's syndrome with mos 45,X/46,X,r(?)

Mos 45,X/46,X,r(?) in 4 patients with Turner's syndrome and no signs of virilization, and in one pair of monozygotic twins, one of them with clitoral hypertrophy, was studied using combined cytogenetic techniques and specially G-11 staining for the characterization of the X or Y origin of the rings. In all 6 patients the ring was G-11 positive, attesting its Y origin. Both twins were operated and bilateral streak gonads with a bilateral nodule of testicular tissue were found. Similar small rings were also studied in one patient with mos 46,XX/46,X,r(X) and in one nonvirilized Turner's syndrome patient with a larger ring; in these two cases the ring was G-11 negative. It seems that the small rings occasionally found in Turner's syndrome are more frequently from Y origin and therefore prophylactic gonadectomy should be considered.     

Serum T3, T4, FT3, TSH and TBG in Turner's syndrome]

Turner's syndrome was originally reported as sexual infantilism, short stature, webbed neck and cubitus valgus. Subsequent investigations, however, have disclosed many other abnormalities both in chromosomal and physical features occurring in this syndrome. An increased prevalence of Hashimoto's thyroiditis in patients with Turner's syndrome has been well documented and molecular defects of the TBG have been described. In our study we examined serum T3, T4, FT3, FT4, TSH and TBG levels in 18 girls with Turner's syndrome, in 18 healthy control girls and in the parents of both groups. We reported significant elevated levels of T3 and FT3 in the Turner's group (P 0.01). We did not find any quantitative abnormalities of immunoreactive TBG in the same patients.     

Evaluation of the parathyroid function in six patients with hypophosphatemic osteomalacia,including a case of tertiary hyperparathyroidism developing during combined oral phosphate and vitamin D therapy

AIM: To describe a case of tertiary hyperparathyroidism after long-term phosphate and vitamin D therapy and the retrospective evaluation of parathyroid function in 6 patients with hypophosphatemic osteomalaica. METHODS: We evaluated the parathyroid function by measuring iPTH before and during treatment and divided the patients into normal and elevated serum iPTH groups. RESULTS: In the normal serum iPTH group, the 4 patients were all males, whereas the 2 patients in the elevated serum iPTH group were females. Clinical characteristics and biochemical results showed no differences between the two groups. One of the women with an elevated iPTH level (224 pg/ml) had a normal serum calcium level and no evidence of increasing parathyroid uptake by (99m)Tc-MIBI scan 52 months after treatment. The other woman also had an elevated iPTH level (483 pg/ml) and a normal serum calcium level 56 months after treatment. However, in this latter case both her iPTH (1,447 pg/ml) and serum calcium (11.3 mg/dl) levels were elevated 113 months after treatment, when a (99m)Tc-MIBI scan showed increased uptake in all four parathyroid glands during early and delayed phases of the scan. Parathyroidectomy was performed after the diagnosis of tertiary hyperparathyroidism was made, and the histological findings showed adenomatous hyperplasia. CONCLUSIONS: Our findings indicate that even with vitamin D therapy, long-term phosphate therapy may lead to the development of secondary or tertiary hyperparathyroidism in hypophosphatemic osteomalacia and, therefore, suggest that it is important to carefully monitor the parathyroid function during therapy in those with hypophosphatemic osteomalacia.     

Undifferentiated embryonal sarcoma of the liver mimicking acute appendicitis. Case report and review of the literature

Background

Parathyroid carcinoma is a rare cause of primary hyperparathyroidism and may be associated with significant disease related morbidity and mortality. Preoperative diagnosis remains a challenge, which may jeopardize appropriate and successful patient treatment.

Case presentation

We report a case of parathyroid carcinoma diagnosed in a 60-year-old woman that presented with a tender nodule located at the left lower thyroid pole and had been present for several years. Ultrasound examination revealed a 2.7 × 1.6 × 2.7 cm mass within the lower left lobe of the thyroid with cystic and solid areas. Lab measurement of the intact PTH level revealed it to be three times the upper limit of normal and the serum calcium level was within normal limits. A left thyroid lobectomy and isthmusectomy was carried out. Histopathological evaluation was diagnostic for a parathyroid carcinoma. At greater than two years of follow-up, the patient has had no evidence of disease recurrence and her serum PTH and calcium levels have remained within normal.

Conclusion

Parathyroid carcinoma is a rare endocrine tumor which must be considered in the differential diagnosis of a nodular thyroid mass. En bloc resection remains the treatment of choice for this malignancy. Disease prognosis is influenced by the extent of the initial resection, the presence of metastases, and adequate long-term follow-up.     

Growth hormone response to growth hormone releasing hormone 1-40 in Turner's syndrome

The response of growth hormone (GH) to acute administration of GH-releasing hormone 1-40 (GHRH) was evaluated in 12 patients with Turner's syndrome and in 12 prepubertal or early pubertal girls. In 7 of 12 patients GHRH induced a definite increase (greater than 10 ng/ml) of plasma GH levels. In 5 patients there was a poor GH rise after GHRH administration (less than 10 ng/ml). Overall, the mean GH response of patients was significantly lower than that of normal girls. Five out of 7 patients with a 45 X,O karyotype had a reduced GH rise after GHRH, while all patients with non X,O karyotype (mosaicism and/or 46 X,iX) had a normal GH response to GHRH. Although the cause of short stature in patients with Turner's syndrome is most likely multifactorial, a reduced pituitary GH reserve, as documented by the reduced GH response to GHRH in some of our patients, may contribute to the growth impairment in this disorder.     

Twenty-four hour plasma GH, FSH and LH profiles in patients with Turner's syndrome

We studied the plasma GH profiles in 6 patients with Turner's syndrome and 6 normal girls of short stature by sampling every 20 min for 24 hours. We observed episodic secretion of GH in these subjects. The mean plasma 24 h GH level in patients with Turner's syndrome was 3.6 +/- 1.4 (SD) ng/ml which was significantly lower than that of normal short girls (7.1 +/- 2.2 ng/ml, p less than 0.01). The GH secretion during both nighttime and daytime was decreased in the patients with Turner's syndrome, however the number of pulses did not differ significantly. There were no correlations between the mean plasma 24 h GH level on one hand and peak GH level obtained after GH provocative test and plasma somatomedin C on the other. Plasma FSH and LH levels were also measured in 4 patients with Turner's syndrome. Both levels were elevated and there observed no clear pulsatile secretion of FSH, but, some pulsatile secretion of LH was observed in two patients. These data indicate that patients with Turner's syndrome have decreased endogenous GH secretion, even though they show normal GH responses to GH provocative tests.     

A case of hyponatremia in panhypopituitarism caused by the primary empty sella syndrome

A 64-year-old woman was admitted for evaluation of hyponatremia. She was maintained on hypertonic saline administration. Without this therapy, the serum Na concentration decreased progressively to 127 mEq/L and the plasma osmolality to 254 mOsm/Kg H2O, on Day 3. At that time, the concentration of antidiuretic hormone (ADH) was as high as 3.5 pg/ml. A skull radiogram revealed an enlarged sella turcica. Computed tomography (CT) revealed a low density in the sella, and magnetic resonance imaging revealed equal intensity of the sella turcica and the cerebrospinal fluid. A diagnosis of empty sella syndrome was made by metrizamide cisternography in conjunction with CT scanning. A diagnosis of panhypopituitarism was made by endocrine function tests. 123I-thyroidal uptake was 6% when her serum TSH was 10.9 microU/ml, suggesting that she might also have primary hypothyroidism. When this patient was given glucocorticoid before levothyroxine replacement, her serum Na concentration rose up to about 140 mEq/L and a normal relationship between her plasma ADH level (2.4 pg/ml) and plasma osmolality (281 mOsm/kg H2O) was restored. Therefore, it was suggested that ADH hypersecretion induced by the glucocorticoid deficiency might in part contribute to the development of hyponatremia. This is the case of primary empty syndrome associated with panhypopituitarism, in whom initial symptom was caused by hyponatremia.     

Cytogenetic findings in Serbian patients with Turner's syndrome stigmata

Cytogenetic findings are reported for 31 female patients with Turner's syndrome. Chromosome studies were made from lymphocyte cultures. Non-mosaicism 45,X was demonstrated in 15 of these patients, whereas only three were apparently mosaic. Eight patients showed non-mosaic and four patients showed mosaic structural aberrations of the X-chromosome. One non-mosaic case displayed a karyotype containing a small marker chromosome. Conventional cytogenetics was supplemented by fluorescence in situ hybridization (FISH) with an X-specific probe to identify the chromosomal origin of the ring and a 1q12-specific DNA probe to identify de novo balanced translocation (1;9) in one patient. To our knowledge, this is the first finding of karyotype 45,X,t(1;9)(cen;cen)/46,X,r(X),t(1;9)(cen;cen) in Turner's syndrome. The same X-specific probe was also used to identify a derivative chromosome in one patient.     

Pulmonary adenocarcinoma, Lambert--Eaton myasthenic syndrome, and voltage-gated calcium channels: a case report

ABSTRACT: INTRODUCTION: Lambert--Eaton myasthenic syndrome is a rare disorder and it is known as a paraneoplastic neurological syndrome. Small cell lung cancer often accompanies this syndrome. Lambert--Eaton myasthenic syndrome associated with lung adenocarcinoma is extremely rare; there are only a few reported cases worldwide. CASE PRESENTATION: A 75-year-old Japanese man with a past history of chronic rheumatoid arthritis and Sjogren syndrome was diagnosed with Lambert--Eaton myasthenic syndrome by electromyography and serum anti-P/Q-type voltage-gated calcium channel antibody level preceding the diagnosis of lung cancer. A chest computed tomography to screen for malignant lesions revealed an abnormal shadow in the lung. Although a histopathological examination by bronchoscopic study could not reveal the malignancy, lung cancer was mostly suspected after the results of a chest computed tomography and [18F]-fluorodeoxyglucose positron emission tomography. An intraoperative diagnosis based on the frozen section obtained by tumor biopsy was adenocarcinoma so the patient underwent a lobectomy of the right lower lobe and lymph node dissection with video-assisted thoracoscopic surgery. The permanent pathological examination was the same as the frozen diagnosis (pT2aN1M0: Stage IIa: TNM staging 7th edition). Immunohistochemistry revealed that most of the cancer cells were positive for P/Q-type voltage-gated calcium channel. CONCLUSIONS: Our case is a rare combination of Lambert--Eaton myasthenic syndrome associated with lung adenocarcinoma, rheumatoid arthritis and Sjogren syndrome, and to the best of our knowledge it is the first report that indicates the presence of voltage-gated calcium channel in lung adenocarcinoma by immunostaining.     

Primary Hyperparathyroidism

ObjectiveTo review primary hyperparathyroidism and the key issues that are relevant to the practicing endocrinologist.MethodsThe latest information on the presentation, diagnosis, and traditional and nontraditional aspects of primary hyperparathyroidism is reviewed.ResultsThe diagnosis of primary hyperparathyroidism is straightforward when the traditional hypercalcemic patient is documented to have an elevated parathyroid hormone (PTH) level. Commonly, patients are identified who have normal serum calcium levels but elevated PTH levels in whom no secondary causes for hyperparathyroidism can be confirmed. Traditional target organs of primary hyperparathyroidism—the skeleton and the kidneys—continue to be a focus in the patient evaluation. Bone mineral density shows a typical pattern of involvement with the distal one-third radius being selectively reduced compared with the lumbar spine in which bone mineral density is generally well maintained. Neurocognitive and cardiovascular aspects of primary hyperparathyroidism, while a focus of recent interest, have not been shown to definitively aid in the decision for or against surgery. The recommendation for surgery in primary hyperparathyroidism is based on guidelines that focus on the serum calcium level, renal function, bone mineral density, and age. In patients who do not meet guidelines, a nonsurgical management approach has merit.ConclusionsPrimary hyperparathyroidism is continuing to show changes in its clinical profile, with normocalcemic primary hyperparathyroidism being a topic of great interest. Skeletal and renal features of primary hyperparathyroidism drive, in most cases, the decision to recommend surgery. In patients who do not meet any criteria for surgery, a conservative approach with appropriate monitoring is acceptable. (Endocr Pract. 2012;18:781-790)     

Fabry's disease: Heterozygote detection by hair root analysis

Summary Serum concentrations of immunoglobulin G (IgG), immunoglobulin M (IgM) and immunoglobulin A (IgA) were determined in 15 women with a lack of X chromosome material (Turner's syndrome), and compared with the immunoglobulin concentrations in normal men and women. Further, the investigation is supplemented by a comparison of normal women and the Turner group matched according to age.The serum concentrations of IgG and IgA in women with Turner's syndrome were very close to the concentration in serum from normal men, whereas the concentration of IgM was significantly lower. Compared to normal women the concentrations of IgG and IgM were significantly lower, and the concentration of IgA significantly higher in the Turner group.Whether these differences in serum immunoglobulins are determined by hormonal factors or under direct genetic control linked to the X chromosomes, is discussed.     

Delayed-Onset Hypoparathyroidism in an Adolescent with Chromosome 22Q11 Deletion Syndrome

ObjectiveTo describe the first case of established chromosome 22q11 deletion syndrome with late onset presentation of hypocalcemia secondary to hypoparathyroidism.MethodsWe present the history, clinical and laboratory investigations, and management of a 17-yearold adolescent boy who presented with 3 separate seizures secondary to hypocalcemia. This patient had an established diagnosis of chromosome 22q11 deletion syndrome at the time of the seizure presentations, but had previously normal calcium levels.ResultsHypocalcemia was noted during each seizure, with corrected calcium levels ranging from 6.64 to 7.76 mg/dL (reference range, 8.52 to 10.52 mg/dL). The hypocalcemia was secondary to hypoparathyroidism, with parathyroid hormone levels < 2.75 pg/mL (reference range, 22.9 to 68.75 pg/mL). He was treated with calcitriol, 0.5 μg daily, and calcium carbonate, 2,400 mg daily, leading to normalization of serum calcium and resolution of seizures.ConclusionChromosome 22q11 deletion syndrome is a relatively common genetic disorder with a wide variety of phenotypic manifestations including cardiac abnormalities, abnormal facies, thymic dysfunction, cleft palate, and hypocalcemia. This case shows that medical practitioners should be aware that hypocalcemia can present after an established diagnosis, which has implications for the management of this disorder. (Endocr Pract. 2011;17: e123-e125)