Bone and joint alterations in acromegaly

Growth hormone (GH) is fundamental for the maintenance of bone mass and metabolism both during childhood and in adulthood. This effect is due to a complex interaction between circulating GH and IGF-I produced peripherally. In vitro data and experimental animal models have clarified many of the regulatory mechanisms underlying the characteristic skeletal changes occurring in acromegaly. This review focuses on the effects of GH excess on bone metabolism and mass in acromegalic patients and, in particular, on the influence of factors such as hypogonadism, gender, age and therapy on bone metabolism and arthropathy.     

Expression of retinoblastoma protein in human growth hormone-secreting pituitary adenomas

The retinoblastoma gene (RB1) is a tumor-suppressor gene in chromosomal region 13q14.2. Its role in the pathogenesis of pituitary tumors has not been fully clarified. Some studies have shown that losses in this chromosomal region are related to aggressive tumor behavior, although the retinoblastoma protein (pRB) is still expressed. Conversely, lack of expression of pRB was observed in one fourth of GH-secreting pituitary adenomas (GH-tumors). In order to further study the expression of pRB in GH-tumors, we evaluated this protein in 49 tumors from patients with acromegaly (20 noninvasive, 25 invasive, and 4 with no information) and 8 normal pituitaries using immunohistochemistry (IHC). Nuclear staining for pRB ranged from 0 to 90% (median 40%) in the tumors and from 40 to 80% (median 58%) in normal pituitaries. In 10 tumors (20% of total) the adenomatous cells were negative (5 cases) or had very low labeling (5 cases) for pRB. Sixty three percent (31/49) of the tumors showed staining in 10–80% of the cells and in 16% (8/49) of the cases >80% of the adenomatous cells were positive for pRB. The expression of pRB was not different in invasive and noninvasive tumors. In conclusion, pRB is underexpressed in a subgroup of GH-tumors, and this may represent an early event in the pathogenesis of this tumor subtype.     

Long-term treatment of acromegalic patients with repeatable parenteral depot-bromocriptine

Summary We studied the efficacy and tolerability of a repeatable long-acting parenteral depot-bromocriptine preparation (Parlodel LAR) in 14 acromegalic patients, 10 of whom had received oral bromocriptine therapy previously, 2 of them showing intolerance to oral bromocriptine. Patients received i.m. injections of 50–100 mg depot-bromocriptine at 4-week intervals for 3–24 months (median 6). Growth hormone profiles were assessed by four daily samples at 4-week intervals. Main daily growth hormone levels decreased from 52.1 ±12.3 g/l (mean ± SEM) to 19.4 ± 4.7 g/l on the day of injection. In 6 patients, growth hormone values were lowered by more than 50%, whereas IGF-I levels decreased only slightly and growth hormone values during the oral glucose tolerance test remained non-suppressible. Tumour sizes were not affected. Two women became pregnant and were delivered of healthy babies. Side-effects typical of bromocriptine occurred frequently on the days of injection and diminished in most patients after 2 months of therapy despite increasing dosage. Compared with previous oral bromocriptine therapy, 9 of 10 patients preferred the depot preparation, whereas the reduction of growth hormone levels was similar during both treatments. In conclusion, depot-bromocriptine should be considered for acromegalic patients intolerant to oral bromocriptine.Abbreviations br Bromocriptine - oral br. oral bromocriptine - depot-br. depot-bromocriptine - GH growth hormone - oGTT oral glucose tolerance test - GnRH gonadotropin-releasing hormone - TRH thyrotropin-releasing hormone     

Sphenoidal sinus mucocele after transsphenoidal surgery for acromegaly

This report concerns one case of a sphenoid sinus mucocele occurring 17 years after transsphenoidal surgery for acromegaly. In 1979, a 51-year-old man was successfully operated by the transnasal transsphenoidal approach for a growth hormone (GH) adenoma 1 cm in diameter. In 1996, the patient was hospitalized for headaches and diplopia. He presented a loss of right visual acuity with paralysis of the right oculomotor nerve. The basal GH level was normal with a satisfactory decrease after oral glucose ingestion. Pituitary sellar radiography showed a disappearance of the posterior clinoid while magnetic resonance imaging revealed the existence of a bilocular, circular, homogeneous lesion of the sphenoid sinus 3 cm in diameter with a posterior and lateral extension. The diagnosis of mucocele was confirmed by surgical treatment, allowing drainage of the mucocele through a transsphenoidal approach. The drained material was composed of sinus epithelium containing many polynuclear and resorptive cells. Postoperatively, the symptoms decreased dramatically, leading to full recovery of visual function and disappearance of the headaches. Apart from the tumor recurrence, the mucocele of the sphenoid sinus can be evoked as a possible long term complication of transsphenoidal sugery for pituitary adenoma. Received: 2 June 1998 / Accepted: 23 February 1999     

Lanreotide autogel-induced acute pancreatitis in a patient with acromegaly

Somatostatin and somatostatin analogues are considered very useful for the treatment of hormone producing tumors and acute variceal bleeding. They have also been proposed for the treatment of acute pancreatitis and for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis although clinical trials have failed to show any efficacy. The authors report the case of a 45-year-old man, recently diagnosed of acromegaly, which developed an acute pancreatitis shortly after his first injection of lanreotide autogel. The patient developed a severe dilatation of his hypocontractile gallbladder with distension of the intra and extrahepatic biliary ducts, the choledochus and the main pancreatic duct, without lithiasis or other abnormalities at the papilla, which resolved spontaneously in a month. We consider that lanreotide most likely induced a functional spasm of the Sphincter of Oddi, with impairment of the biliary-pancreatic outflow, leading to an acute pancreatitis, and review the literature concerning this drug related pancreatitis.     

Pituitary disease and anaesthesia

Patients with pituitary gland tumours comprise a significant proportion of the neurosurgical population, making transsphenoidal pituitary surgery a relatively common procedure. Such patients present anaesthetists with unique challenges resulting from hormone hypersecretion, pituitary hypofunction or tumour mass effect. To understand this pathophysiology requires a good working knowledge of normal pituitary anatomy and physiology. An appreciation of the respiratory and cardiovascular comorbidities associated with pituitary tumours is also essential to the anaesthetist. We aim to review the key principles involved in the preoperative assessment, intraoperative management and postoperative care of these patients.     

Differentiated thyroid carcinoma in sporadic and familial presentations of acromegaly: A case series

BackgroundIn acromegaly, chronic growth hormone (GH) and insulin-like growth factor-1 (IGF-1) exacerbate comorbidities in multiple organs. Differentiated thyroid carcinoma (DTC) has been reported as being a comorbid condition in acromegaly. Acromegaly is usuallysporadic, but 5% of cases may be genetic. The most frequent inheritable form of acromegaly is related to germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. Epidemiological data on the relationship between active acromegaly, its familial forms and DTC are sparse. We present the investigation of a FIPA family (familial isolated pituitary adenoma) with homogeneous acromegaly and 6 sporadic acromegaly patients with DTC.Patients and methodsA study of 59 acromegaly patients assessed thyroid nodules on ultrasound and fine-needle aspiration biopsy following the ATA 2015 criteria. We diagnosed 7 differentiated thyroid carcinomas. Resected thyroid carcinoma tissues were stained using an anti-AIP antibody. Analysis of germline and tumor-derived DNA for variants in the AIP and MEN1 genes were performed in the FIPA kindred.ResultsWe describe one FIPA patient and 6 sporadic acromegaly cases with DTC. The FIPA family (AIP mutation negative) consisted of two sisters, one of whom had a DTC with intermediate risk and incomplete structural response to therapy. In our study, DTC in sporadic acromegaly had a low recurrence rate (6/6), and excellent response to therapy (6/6). Immunohistochemistry for AIP showed similar or increased staining intensity in DTC versus normal thyroid tissue.ConclusionIn our cohort of sporadic and familial forms of acromegaly with DTC, AIP did not appear to influence thyroid cancer progression.     

Endoscopic Decompression for Optic Neuropathy in McCune-Albright Syndrome

McCune-Albright syndrome (MAS) is characterized by a triad of poly/monostotic fibrous dysplasia, café-au-lait macules and hyperfunctioning endocrinopathies including human growth hormone excess. Acromegaly as a manifestation of endocrine hyperfunction with MAS is uncommon. Surgical excision may be challenging due to the associated severe fibrous dysplasia of the skull base. Through the endoscopic procedures, we treated a case of MAS presenting with compressive optic neuropathy due to fibrous dysplasia and acromegaly caused by growth hormone secreting pituitary adenoma. We reviewed the literature on GH excess in MAS to highlight its surgical and medical challenges.     

Human growth hormone as a regulator of blood glucose concentration and as a diabetogenic substance

Summary Human growth hormone (HGH) has recently been shown to play a prominent role in the control of blood glucose homeostasis. Furthermore, it has long been known that administration of growth hormone in animals can induce a diabetes-like state. In human subjects, exogenous administration of HGH or hypersecretion of the endogenous hormone in acromegaly is accompanied by glucose intolerance in only about 25 per cent of the cases. — In this paper, data are presented which give a more diversified picture of the so-called diabetogenic action of HGH. It is suggested that HGH, although decreasing the peripheral utilization of glucose, is not a primary diabetogenic factor, since its insulinogenic action causes a compensatory hyperinsulinism, with normal glucose tolerance as the result. HGH is diabetogenic only in prediabetic subjects whose pancreas is unable to respond to the insulinogenic effect of the hormone. In such subjects, the diabetogenic action of HGH not being counterbalanced by a compensatory hyperinsulinism, glucose intolerance may result. Thus, HGH may be regarded as anadditional factor for the development of diabetes, the major prerequisite being a preëxisting prediabetic state.Presented as an invited lecture at the VI Acta Endocrinologica Congress, Helsinki, Finland, August 8th–12th, 1967.     

Pathology,pathophysiology, and treatment strategies of endocrine disorders and their cardiac complications

The cardiovascular system is affected by a multitude of endocrine disorders, including dysfunction of the thyroid, calcium, glucocorticoids, insulin/glucose, and growth hormone axes. Since most of these changes in the cardiovascular system are reversible when treated, early diagnosis is important, as if left untreated, they may become fatal. This review focuses on the pathophysiology, clinical presentation, pathology, and treatment of patients with these endocrine diseases who present with a variety of cardiovascular manifestations. Neuroendocrine tumors presenting with the carcinoid syndrome and their cardiovascular manifestations are also discussed.