Nigel Glynn

The natural history of surgically treated but radiotherapy‐naïve nonfunctioning pituitary adenomas

Background and objectives  Transsphenoidal surgery is indicated for patients with nonfunctioning pituitary adenomas (NFPAs) causing compressive symptoms. Previous studies attempting to define the rate of recurrence/regrowth of surgically treated but radiation‐naïve NFPAs were somewhat limited by selection bias and/or small numbers and/or lack of consistency of findings between studies. A better understanding of the natural history of this condition could allow stratification of recurrence risk and inform future management. We aimed to define the natural history of a large, mainly unselected cohort with surgically treated, radiotherapy (RT)‐naïve NFPAs and to try to identify predictors of recurrence/regrowth.

Which patient requires neuroendocrine assessment following traumatic brain injury, when and how?

Traumatic brain injury (TBI) is an important public health problem, particularly among young adults in industrialized countries. Hypopituitarism is a common occurrence among survivors of TBI and may contribute to the associated morbidity seen in the acute and chronic phases following injury. The available data suggest that survivors of moderate to severe TBI should undergo screening for hypopituitarism particularly in the first year after injury. This requires a close liaison between endocrinologists, neurosurgeons, neuropsychologists, intensive care and rehabilitation physicians. Patients who suffer milder forms of TBI should also be considered for endocrine evaluation if they exhibit any clinical features of pituitary hormone deficiencies.

Diagnosing Growth Hormone Deficiency in Adults

Adult growth hormone (GH) deficiency is a recognised syndrome associated with adverse phenotypic, metabolic, and quality-of-life features which improve in many patients when GH is substituted. The appropriate selection of patients at risk of growth hormone deficiency (GHD) is the crucial first step in arriving at a correct diagnosis. Although multiple diagnostic modalities are available including a 24-hour serum GH profile, stimulated GH levels, and insulin-like growth factor-1 (IGF-1) levels, the use of dynamic tests for GH reserves is required in most cases. This paper discusses the utility and drawbacks of the various testing modalities with reference to international guidelines. Regardless of the test chosen, clinical pitfalls including age and obesity must be taken into account. In addition, there is considerable analytical variation in the biochemical measurements of GH and IGF-1 which must be considered before making a diagnosis of GHD in adulthood.

The utility of 99mTc-sestamibi scintigraphy in the localisation of parathyroid adenomas in primary hyperparathyroidism.

BackgroundThere are conflicting data in the literature about the sensitivity of sestamibi scintigraphy in parathyroid tumour localisation in primary hyperparathyroidism (PHPT).AimWe aimed to evaluate the overall sensitivity of this modality in parathyroid tumour localisation and to determine clinical and biochemical factors which influence sensitivity of this method.MethodsWe performed a retrospective review of 57 patients with a biochemical diagnosis of PHPT who had sestamibi scintigraphy performed.ResultsThe sensitivity of sestamibi scanning was 56% in whole group and 63% in those without nodular thyroid disease. Among the patients with confirmed single gland disease (biochemical cure after surgical removal of a single adenoma), sensitivity was 71%. A positive scan was associated with younger age, greater adenoma weight and higher pre-operative serum calcium. Concordance between the sestamibi and neck ultrasonography was 92% accurate in pre-operative tumour localisation.ConclusionSestamibi scintigraphy was more likely to be positive in younger patients without nodular thyroid disease who have larger parathyroid adenomas with more severe hyperparathyroidism.

Unexpected clinical course during treatment of a TSH-secreting pituitary adenoma.

OBJECTIVE To report the rare occurrence of a patient with thyrotropinoma that transitioned into a secretory thyro-somatotroph adenoma during medical treatment with somatostatin analogue. METHODS We report the case of a patient with a thyrotroph pituitary adenoma who developed de novo evidence of growth hormone cosecretion following one year of successful medical treatment. RESULTS A 78-year-old woman was diagnosed with a thyroid stimulating hormone (TSH) secreting pituitary macroadenoma (TSHoma) based on classical clinical and biochemical features. There was no clinical or biochemical evidence of growth hormone (GH) cosecretion. She declined surgical resection and was treated with primary medical therapy, octreotide long acting repeatable (LAR), to which she had an antitumor and antisecretory response; however, following 12 months of successful medical treatment she developed de novo hypersecretion of growth hormone despite involution of the tumor mass. TSH-secreting pituitary adenomas may rarely become plurihormonal during apparently successful medical treatment. This may represent an unusual form of secondary resistance to somatostatin analogue or the rarer phenomenon of tumor transformation into a secretory thyro-somatotroph adenoma. CONCLUSION The unexpected clinical course of this case highlights the need for careful long-term surveillance in patients with TSH secreting pituitary adenomas.

Serum prolactin concentration at presentation of non-functioning pituitary macroadenomas

Objective: Serum PRL levels at presentation may be useful in distinguishing between disconnection hyperprolactinemia in non-secretory pituitary adenomas and prolactinomas in order to guide appropriate therapy; however, there is a debate regarding the discriminatory PRL thresholds. We aimed to examine PRL concentrations at presentation in a cohort of histologically proven non-functioning pituitary adenomas (NFPA). Design and methods: Retrospective case note analysis was performed. Clinical, biochemical, histopathological and radiological data were recorded and analyzed. Complete data were available for 250 subjects with NFPA. Results: Of the study population, 44.8% were hyperprolactinemic at presentation, 55.3% of whom were female. Of those with hyperprolactinemia, 73.2% had PRL<1000 mIU/l on presentation, 24.1% had PRL between 1000 and 1999 mIU/l. Only 2.7% (no.=3 females, 1.2% whole cohort) had PRL>2000 mIU/l (94.3 ng/ml), 2 of whom were pregnant. No male subject and no subjects with an intrasellar macroadenoma had serum PRL>1000 mIU/l (47.2 ng/ml). Overall, serum PRL was not higher among 43 subjects taking medications known to raise PRL. Conclusions: Our data support recent evidence that the serum PRL concentration is rarely >1000 mIU/l in males, or >2000 mIU/l in females, with non-functioning macroadenomas and that, once other contributing factors to the hyperprolactinemia have been excluded, a trial of dopamine agonist therapy for such lesions is indicated.

The effect of growth hormone replacement on the thyroid axis in patients with hypopituitarism: in vivo and ex vivo studies.

Alterations in the hypothalamic–pituitary–thyroid axis have been reported following growth hormone (GH) replacement. The aim was to examine the relationship between changes in serum concentration of thyroid hormones and deiodinase activity in subcutaneous adipose tissue, before and after GH replacement.

Late Recovery of Cranial Diabetes Insipidus following Pituitary Surgery

Background: Diabetes insipidus (DI) is common following surgery for a pituitary/sellar lesion. Postoperative DI persisting beyond a few weeks is usually regarded as permanent, requiring lifelong desmopressin therapy. Case Presentation: A 16-year-old girl underwent pituitary decompression following a pituitary tumour apoplexy. She developed DI with thirst and hypotonic polyuria in the immediate post-operative period, which was controlled with parenteral DDAVP. Her symptoms persisted and she was discharged on oral desmopressin. Subsequently, she commenced growth hormone replacement. A water deprivation test 6 weeks postoperatively confirmed persistent DI with failure to concentrate urine after 8 hours of dehydration. She was maintained on desmopressin and reported intense thirst and polyuria every time she delayed taking the medication up until 1 year postoperatively. After 1 year, she complained of bloating and stopped taking desmopressin but her symptoms did not recur. A repeat water deprivation test confirmed very late resolution of DI with normal urinary concentration. She has remained asymptomatic ever since. Conclusion: Delayed recovery of normal posterior pituitary function is exceptionally rare. We hypothesise that the underlying mechanism may be the revascularisation and regeneration of the posterior pituitary tissues or of the axons terminating in the posterior pituitary.

ALTERATIONS IN THYROID HORMONE LEVELS FOLLOWING GROWTH HORMONE REPLACEMENT EXERT COMPLEX BIOLOGICAL EFFECTS

OBJECTIVE Alterations in the thyroid axis are frequently observed following growth hormone (GH) replacement, but uncertainty exists regarding their clinical significance. We aimed to compare fluctuations in circulating thyroid hormone levels, induced by GH, to changes in sensitive biological markers of thyroid hormone action. METHODS This was a prospective observational clinical study. Twenty hypopituitary men were studied before and after GH replacement. Serum thyroid-stimulating hormone (TSH), thyroid hormones, and insulin-like growth factor 1 were measured. Changes in thyroid hormone concentrations were compared to alterations in resting metabolic rate and cardiac time intervals. Health-related quality of life (QOL) was assessed by disease-sensitive and generic questionnaires. RESULTS Following GH replacement, free thyroxine concentration declined and free triiodothyronine level increased. Resting energy expenditure increased, particularly in subjects with profound hypopituitarism, including TSH deficiency (16.73 ± 1.75 kcal/kg/min vs. 17.96 ± 2.26 kcal/kg/min; P = .01). Alterations in the thyroid axis were more pronounced in subjects with a low/normal baseline respiratory quotient (RQ) who experienced a paradoxical rise in RQ (0.81 vs. 0.86; P = .01). Subjects with a high baseline RQ experienced a slight but nonsignificant fall in RQ without alteration in thyroid axis. The isovolumetric contraction time was shortened during the study; however, this did not reach statistical significance. Improvements in QOL were observed despite alterations in thyroid axis. CONCLUSION Changes in the thyroid axis following GH replacement are associated with complex tissue-specific effects. These fluctuations may induce a hypothyroid phenotype in some tissues while appearing to improve the biological action of thyroid hormone in other organs. ABBREVIATIONS AGHDA = Assessment of Growth Hormone Deficiency in Adulthood; CHOox = carbohydrate oxidation; ET = ejection time; fT3 = free triiodothyronine; fT4 = free thyroxine; GH = growth hormone; GHD = growth hormone deficiency; HB-RQ = high baseline respiratory quotient; HPT = hypothalamic-pituitary-thyroid; ICT = isovolumetric contraction time; IGF-1 = insulin-like growth factor 1; IRT = isovolumetric relaxation time; LB-RQ = low baseline respiratory quotient; LV = left ventricular; NHP = Nottingham Health Profile; QOL = quality of life; REE = resting energy expenditure; RQ = respiratory quotient; rT3 = reverse triiodothyronine; SF-36 = Short Form 36; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; T4 = thyroxine; TT3 = total triiodothyronine; TT4 = total thyroxine.

VARIABLE THYROID-STIMULATING HORMONE DYNAMICS IN 'SILENT' THYROTROPH ADENOMAS

ABSTRACT Objective: Pituitary adenomas that produce thyroid-stimulating hormone (TSH) are typically accompanied by hyperthyroxinemia and a non-suppressed or elevated TSH at diagnosis. Occasionally, patients with this type of tumor have normal thyroid function test results, a condition termed ‘silent’ thyrotroph adenomas. This report characterizes TSH dynamics in this rare pituitary tumor subtype. Methods: We report 2 cases of pituitary macroadenoma associated with visual failure and hypopituitarism. The patients had normal thyroid function test results but the adenoma was intensely immunopositive for β-TSH expression. The results of TSH dynamics are reported for both cases. Results: Preoperative assessment did not reveal any clinical or biochemical evidence of pituitary hormone excess save mild, asymptomatic hyperprolactinemia consistent with pituitary stalk compression. In particular, thyroid function test results were within normal ranges. In both cases, each patients vision recovered following transsp...