PITUITARY IMAGING BY MRI AND ITS CORRELATION WITH BIOCHEMICAL PARAMETERS IN THE EVALUATION OF MEN WITH HYPOGONADOTROPIC HYPOGONADISM.

Objective: A significant ambiguity still remains about which patient deserves a magnetic resonance imaging (MRI) scan of the pituitary during evaluation of hypogonadotropic hypogonadism (HH) in men. Methods: Retrospective case series of 175 men with HH referred over 6 years. Results: A total of 49.7% of men had total testosterone (TT) levels lower than the Endocrine Society threshold of 5.2 nmol/L. One-hundred forty-two patients (81.2%) had normal appearance of pituitary MRI, whereas others had different spectrum of abnormalities (empty sella [n = 16], macroadenoma [n = 8], microadenoma [n = 8], and pituitary cyst [n = 1]). In men with TT in the lowest quartile, MRI pituitary findings were not significantly different from men in the remaining quartiles (P = .50). Patients with raised prolactin had higher number of abnormal MRI findings (38.9% vs. 13.7%; P = .0014) and adenomatous lesions (macro and micro) (27.8% vs. 4.3%; P = .01) in comparison to men with normal prolactin. The prolactin levels (median [interquartile range]) were highest in men with macroadenomas in both groups (9,950 [915]; P = .007 and 300 [68.0] mU/L; P = .02, respectively), with concomitant lower levels of other pituitary hormones. Multivariate logistic regression showed an association of abnormal pituitary MRI with insulin-like growth factor 1 (IGF-1) standard deviation score (SDS) (odds ratio [OR], 1.78 [95% confidence interval (CI), 1.15 to 2.77]; P = .009) and prolactin (OR, 1.00 [95% CI, 1.00 to 1.03]; P = .01). Conclusion: MRI of the pituitary is not warranted in all patients with HH, as the yield of identifiable abnormalities is quite low. Anatomic lesions are likely to be present only when low levels of TT (<5.2 nmol/L) are found concomitantly with high levels of prolactin and/or low IGF-1 SDS. Abbreviations: CI = confidence interval; FT4 = free thyroxine; GH = growth hormone; HH = hypogonadotropic hypogonadism; IGF-1 = insulin-like growth factor; LH = luteinizing hormone; MRI = magnetic resonance imaging; OR = odds ratio; SDS = standard deviation score; TSH = thyroid-stimulating hormone; TT = total testosterone.

GRANULOMATOUS DISEASE OF UNUSUAL SITES CAUSING HYPERCALCEMIA: TWO CASE REPORTS.

OBJECTIVE: Hypercalcemia with suppressed parathyroid hormone (PTH) levels is mostly due to granulomatous disease (GD) or neoplastic disease. In GD, autonomous activity of extra-renal 1α-hydroxylase enzyme is usually the underlying cause. We describe a pair of cases where hypercalcemia resulted from GD of unusual sites posing significant diagnostic challenges. METHODS: We describe 2 cases of PTH-independent hypercalcemia due to GD of the prostate gland and the stomach. RESULTS: Both cases presented with marked hypercalcemia and suppressed PTH levels. Case 1 is an elderly male who presented with marked symptomatic hypercalcemia on multiple occasions. Investigations revealed elevated levels of 1,25-dihydroxyvitamin D3 and prostate-specific antigen but normal PTH-related protein. Transrectal biopsy of the prostate gland confirmed the presence of chronic granulomatous prostatitis. The patient responded very well to steroids which entirely normalized his calcium level. Case 2 is a male who presented similarly with significant hypercalcemia but had upper gastrointestinal symptoms and anemia at onset. Endoscopy and biopsy established the presence of granulomatous gastritis likely due to Crohn disease which responded to steroids resulting in normalization of calcium levels within a short span of time. CONCLUSION: While the majority of PTH-independent hypercalcemia cases are due to GDs of lymph nodes or malignancy, our cases indicate that in uncertain cases, granulomatous processes involving unusual sites should be considered in the evaluation of hypercalcemia with suppressed PTH.

Relationship between serum thyrotropin and urine albumin excretion in euthyroid subjects with diabetes.

BACKGROUND: Microalbuminuria represents vascular and endothelial dysfunction. Thyroid hormones can influence urine albumin excretion as it exerts crucial effects on the kidney and on the vascular system. This study explores the relationship between serum thyrotropin and urine albumin excretion in euthyroid patients with diabetes. METHODS: A total of 433 patients with type 1 or 2 diabetes were included in this retrospective cross-sectional study. Data included anthropometric measurements and biochemical parameters from diabetes clinic. Males with urine albumin creatinine ratio >2.5 and female's >3.5 mg/mmoL were considered to have microalbuminuria. RESULTS: 34.9% of the patients had microalbuminuria. Prevalence of microalbuminuria increased according to TSH quartiles (26.9, 34.6, 38.5 and 44.9%, P for trend = 0.02). In a fully adjusted logistic regression model, higher TSH concentrations were associated with high prevalence of microalbuminuria (adjusted odds ratio 2.06 [95% CI: 1.14-3.72]; P = 0.02), while comparing the highest with the lowest quartile of TSH. Multiple linear regression analysis showed an independent association between serum TSH and urine albumin creatinine ratio (ß = 0.007, t = 2.03 and P = 0.04). The risk of having microalbuminuria was higher with rise in TSH concentration in patients with younger age (<65 years), raised body mass index (≥25 kg/m2), hypertension, type 2 diabetes and hyperlipidaemia and age was the most important determinant ( P for interaction = 0.02). CONCLUSION: Serum TSH even in the euthyroid range was positively associated with microalbuminuria in euthyroid patients with diabetes independent of traditional risk factors. This relationship was strongest in patients with components of the metabolic syndrome.

Cinacalcet: A Viable Therapeutic Option for Primary Hyperparathyroidism in the Elderly.

OBJECTIVE: Parathyroidectomy is usually curative in primary hyperparathyroidism (PHPT), but its utility would be limited if patients are elderly who may either refuse surgery or may have advanced frailty and multimorbidity. We evaluated the effectiveness of cinacalcet, an allosteric modulator of calcium-sensing receptor in PHPT in an elderly cohort of patients. METHODS: A prospective analysis of 29 patients who had PHPT and despite fulfilling criteria for surgery were unable to undergo parathyroidectomy either due to self-refusal (n = 12) or due to advanced multimorbidity (n = 17). All patients completed treatment with cinacalcet for at least for 6 months. Analysis were performed as per age (<75 and ≥75 years) and Charlson comorbidity index (CCI) score (≤5 and >5). RESULTS: Our patients were the elderly (77 ± 12.7 years). In the whole group, complete normocalcemia was observed in 72.4% of patients (mean reduction: -0.55 mmol/l [confidence interval (CI) 0.4--0.7; P < 0.0001]) and parathormone (PTH) normalized (≤6.9 pmol/l) in 33.4% of patients [mean reduction: -5.5 pmol/l (CI -11.6-0.6; P = 0.0015)]. In subgroup analysis, the severity of hypercalcemia was found to be higher patients with age <75 years and also in patients with CCI score >5. Cinacalcet lowered adjusted calcium in both age groups (P < 0.0001) with a greater reduction (20.5% vs. 16.2%; P < 0.0001 for both) in patients with CCI score >5. PTH fell in both age groups but significantly (-6.7 pmol/l [CI -14.9-1.5]; P = 0.008) in ≥ 75 years category and likewise, the drop was greater in patients with higher CCI scores (-7.1 pmol/l [CI -15.8-1.6); P = 0.009] vs. [-4.5 pmol/l [CI -3.9--5.10]; P = 0.001). Patients with age <75 years and with CCI score ≤5 needed higher doses of cinacalcet to achieve biochemical targets. CONCLUSION: Cinacalcet is a viable and valuable treatment strategy for elderly patients with multiple comorbidities who suffer from PHPT but either cannot or refuse to undergo parathyroidectomy.

Maturation in Serum Thyroid Function Parameters Over Childhood and Puberty: Results of a Longitudinal Study.

Context: Serum thyroid hormone levels differ between children and adults, but have not been studied longitudinally through childhood. Objective: To assess changes in thyroid-stimulating hormone (TSH) and thyroid hormone levels over childhood and their interrelationships. Design: Cohort study. Setting: The Avon Longitudinal Study of Parents and Children, a population-based birth cohort. Participants: A total of 4442 children who had thyroid function measured at age 7, and 1263 children who had thyroid function measured at age 15. Eight hundred eighty-four children had measurements at both ages. Main Outcome Measures: Reference ranges for TSH, free tri-iodothyronine (FT3), free thyroxine (FT4), their longitudinal stability, and interrelationships. Results: Children at age 7 years had a higher FT3 [6.17 pmol/L, standard deviation (SD) 0.62] than children at age 15 (5.83 pmol/L, SD 0.74); P < 0.0001 with 23.2% of children at age 7 having FT3 above the adult reference range. Higher FT3 levels at age 7 in boys (P = 0.0001) and girls (P = 0.04) were associated with attainment of a more advanced pubertal stage at age 13. TSH was positively associated with FT3 at age 7 and age 15 even after adjusting for confounders. In contrast, TSH was negatively associated with FT4. Conclusions: There are substantial changes in TSH and thyroid hormone levels over childhood, in particular for FT3, which appear to relate to pubertal readiness. Our data provide increased insight into the evolution of the pituitary-thyroid axis over childhood and may have implications for determining optimal ranges for thyroid hormone replacement in children.