Natural history of non-functioning pituitary microadenomas: results from the UK non-functioning pituitary adenoma consortium.

OBJECTIVE: The optimal approach to the surveillance of non-functioning pituitary microadenomas (micro-NFPAs) is not clearly established. Our aim was to generate evidence on the natural history of micro-NFPAs to support patient care. DESIGN: Multi-centre, retrospective, cohort study involving 23 endocrine departments (UK NFPA consortium). METHODS: Clinical, imaging, and hormonal data of micro-NFPA cases between January, 1, 2008 and December, 21, 2021 were analysed. RESULTS: Data for 459 patients were retrieved [median age at detection 44 years (IQR 31-57)-152 males/307 females]. Four hundred and nineteen patients had more than two magnetic resonance imagings (MRIs) [median imaging monitoring 3.5 years (IQR 1.71-6.1)]. One case developed apoplexy. Cumulative probability of micro-NFPA growth was 7.8% (95% CI, 4.9%-8.1%) and 14.5% (95% CI, 10.2%-18.8%) at 3 and 5 years, respectively, and of reduction 14.1% (95% CI, 10.4%-17.8%) and 21.3% (95% CI, 16.4%-26.2%) at 3 and 5 years, respectively. Median tumour enlargement was 2 mm (IQR 1-3) and 49% of micro-NFPAs that grew became macroadenomas (nearly all >5 mm at detection). Eight (1.9%) patients received surgery (only one had visual compromise with surgery required >3 years after micro-NFPA detection). Sex, age, and size at baseline were not predictors of enlargement/reduction. At the time of detection, 7.2%, 1.7%, and 1.5% patients had secondary hypogonadism, hypothyroidism, and hypoadrenalism, respectively. Two (0.6%) developed hypopituitarism during follow-up (after progression to macroadenoma). CONCLUSIONS: Probability of micro-NFPA growth is low, and the development of new hypopituitarism is rare. Delaying the first follow-up MRI to 3 years and avoiding hormonal re-evaluation in the absence of tumour growth or clinical manifestations is a safe approach for micro-NFPA surveillance.

Isolated splenic sarcoidosis: a rare cause of hypercalcaemia in a patient with type 1 diabetes.

A 30-year-old man was admitted to Intensive Therapy Unit (ITU) with status epilepticus secondary to severe hypoglycaemia on a background of type 1 diabetes. CT of the brain showed generalised cerebral oedema. He was successfully stepped down to a medical ward after 2 weeks. He was noted to have persistently high calcium, which required multiple doses of pamidronate. Parathyroid hormone level was appropriately low. CT of the thorax, abdomen and pelvis showed mild hepatosplenomegaly with small pathological lymph nodes throughout the abdomen. Bone marrow biopsy was unremarkable. Lymph node biopsy was difficult to achieve, and therefore a positron emission tomography scan was arranged. This showed an enlarged and hypermetabolic spleen. Differential diagnoses at this point included lymphoma and sarcoidosis. He underwent diagnostic splenectomy, and the diagnosis of sarcoidosis was confirmed histologically. Calcium level remained normal 17 months after splenectomy.

Pituitary infundibular epidermoid cyst: a rare cause of hypopituitarism.

A 53-year-old man presented with 6 months history of weight loss associated with nausea, fatigue, dizziness and headache. On arrival he was in adrenal crisis. Biochemistry revealed anterior hypopituitarism with low cortisol, thyroxine, testosterone and a slightly raised prolactin. He was commenced on steroids, thyroxine and testosterone. MRI pituitary gland was reported to have a 9.4 mm microadenoma. Cabergoline was started for a possible microprolactinoma. Follow-up MRI showed increase in the size of complex cystic lesion causing chiasmal compression raising a possibility of craniopharyngioma. Visual fields assessment was normal. In view of the rapid enlargement, to protect vision and obtain a tissue diagnosis he underwent endoscopic trans-sphenoidal surgery. A cystic lesion was noted intraoperatively originating from pituitary stalk with intrasellar and suprasellar extension. It was filled with white caseous material and fluid. Histology revealed epidermoid cyst. His headache resolved postoperatively.

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.

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.