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PubMed1989

Marked elevation of serum dehydroepiandrosterone sulphate in Cushing's disease with macronodular adrenocortical hyperplasia.

A 30-year-old man presented with longstanding hypercortisolism and biochemical studies typical of pituitary-dependent Cushing's disease. After unsuccessful transsphenoidal surgery, plasma ACTH transiently became undetectable and adrenal computed tomography (CT) was consistent with macronodular hyperplasia. Serum dehydroepiandrosterone sulphate (DHEA-S) exceeded 10,000 ng/ml (normal 2,000-3,350 ng/ml). Despite either transient adrenal autonomy or variable adrenocortical ACTH hyperresponsiveness, urinary cortisol normalized within eight months following pituitary irradiation alone. Serum DHEA-S fell progressively but remained mildly elevated (4,000 ng/ml). Follow-up CT showed minimal residual adrenal nodularity. Given these findings and a review of the literature, we propose that chronic cosecretion of non-ACTH proopiomelanocortinderived peptides may have stimulated both hypersecretion of DHEA-S and adrenocortical macronodularity in this patient.

Adrenal Cortex Diseases↗

PubMed2004

Successful treatment of childhood-onset Cushing's disease is associated with persistent reduction in growth hormone secretion.

OBJECTIVE: Although Cushing's disease (CD) rarely occurs in childhood, affected children commonly fail to achieve predicted adult height. Hypercortisolaemia results in reduced GH secretion and GH-deficiency may persist or demonstrate delayed recovery after successful treatment of CD in adults. Whether recovery of spontaneous GH secretion occurs following treatment of childhood CD has yet to be established. DESIGN AND PATIENTS: We performed a retrospective analysis of the GH status of 13 children (10 males; 12.8 +/- 1.0 years, mean +/- SE) who had undergone successful treatment of CD that occurred prior to the completion of linear growth. Each underwent transsphenoidal hypophysectomy, resulting in satisfactory control of glucocorticoid levels in 7/13 (54%). The remaining six patients (46%) received fractionated external beam irradiation (4500 Gy). At the time of GH assessment, circadian dynamics of cortisol were normal in eight patients and five were receiving titrated glucocorticoid replacement. MEASUREMENTS: GH status was assessed using the peak response to a provocative stimulus. Eleven out of 13 underwent testing with insulin-induced hypoglycaemia (nadir plasma glucose </= 2.2 mmol/l) and glucagon provocation was used in 2/13. Severe GH-deficiency was defined as a peak GH response < 9 mU/l, and a normal response as > 30 mU/l. Intermediate values were taken to represent subnormal GH status. Assessment of GH status was performed 39 +/- 10 months (median +/- SE) following successful treatment (range 9-108 months). RESULTS: Using these criteria 4/13 (31%) patients had severe GH-deficiency. Only 2/13 (15%) had a normal response. 7/13 (54%) achieved peak GH levels in the subnormal range. Those with multiple pituitary hormone deficiencies were most likely to have lower peak GH levels, but there was no clear effect of pituitary irradiation or relationship between duration post cure and peak GH response. CONCLUSION: GH-deficiency is common and may persist for many years following successful treatment of CD prior to completion of linear growth. External radiotherapy does not necessarily result in severe GH-deficiency in the short term. Assessment of GH status and consideration of GH treatment should be considered following treatment of CD in childhood and adolescence in order to maximize the opportunities to achieve a satisfactory final adult height. In those with subnormal GH responses, continued assessment is necessary to determine whether the GH axis subsequently recovers or if these patients develop features of the adult GH-deficiency syndrome.

Adolescent↗

PubMed1979

Cushing's disease: megadose dexamethasone suppression in a case refractory to medical therapy.

A patient with Cushing's disease failed to show complete suppressibility of adrenal function with conventional "high" doses of dexamethasone (8 mg per day). Higher doses were required to achieve suppression. Pituitary irradiation and medical therapy (cyproheptadine, metyrapone, and aminoglutethimide) failed to control the disease, necessitating bilateral adrenalectomy. The diagnostic and therapeutic implications of megadose dexamethasone suppression have not been clearly addressed in the medical literature. It is possible that adrenal suppression achieved only with unconventionally high doses of steroids may be predictive of refractoriness to nonsurgical therapy.

17-Hydroxycorticosteroids↗

PubMed1980

The treatment of acromegaly by transsphenoidal surgery.

Pituitary tumors were removed transsphenoidally in 32 patients with acromegaly. Ten patients had high prolactin (PL) levels as well as elevated growth hormone (GH) levels. In 24 patients, GH levels were lowered to 5 ng/mL or less and remained low. The PL level was reduced to normal in eight patients. Of three patients with postoperative GH levels of 6 to 10 ng/mL, one patient remains in this range but two have relapsed. Five patients showed only a partial lowering in GH level. Pituitary irradiation lowered the level further. Hypopituitarism developed in four patients. Permanent diabetes insipidus occurred in one patient and meningitis developed in another. They subsequently recovered. There were no deaths. Abnormal GH responses to hyperglycemia, hypoglycemia, and levodopa returned to normal following surgery. Transsphenoidal tumor removal appears to be an effective treatment for acromegaly.

Acromegaly↗

PubMed1986

The long-term effects of megavoltage radiotherapy as sole or combined therapy for large prolactinomas: studies with high definition computerized tomography.

The long-term sequelae of external pituitary irradiation alone or in combination with surgery and/or bromocriptine therapy have been studied in 14 patients with large prolactinomas over an observation period of 6-22 years (mean 13 years). Galactorrhoea was abolished in four of the five females with this symptom, but menstrual disturbance persisted in five of six patients. Sexual function was normal without sex hormone replacement in only one of the eight males after treatment. Neurological deficits were abolished or improved by treatment in all 9 patients with this presentation. Serum prolactin levels declined after treatment (P less than 0.001) and fell to within the normal range off bromocriptine therapy in six of the 14 patients at a mean of 9 years (range 5-17 years) after radiotherapy. All patients had anterior pituitary deficiency of some degree at reassessment, and 13 required replacement treatment. Serial skull radiographs revealed remineralization of the fossa floor in five patients and a decrease in fossa size in three. All five patients who did not also have surgery had evidence of tumour shrinkage without bromocriptine treatment (on CT scan or metrizamide cisternography). Fourth generation CT scans on completion of the study revealed a decrease in tumour mass in all patients, with varying degrees of empty sella in 13 and a cystic intrasellar tumour in the remaining one. Residual tumour was demonstrated in 10 patients, three of whom had normal serum prolactin levels, while one patient without visible tumour had persistent hyperprolactinaemia. Radiotherapy, alone or in combination with surgery and bromocriptine, effectively decreases prolactin secretion and tumour size in patients with large prolactinomas at the expense of other anterior pituitary function. Circulating prolactin levels are a poor marker of residual tumour volume.

Adolescent↗

PubMed1986

Cushing's disease coexisting with a single macronodule simulating adenoma of the adrenal cortex.

A rare case of Cushing's disease coexisting with a single macronodule simulating adenoma of the adrenal cortex is presented. The basal and dynamic tests supported the diagnosis of Cushing's disease, whereas the CT-scan, ultrasound and iodocholesterol uptake were suggestive of a left adrenal adenoma. Treatment consisted of extirpation of the nodular gland followed by pituitary irradiation. The examination revealed a single macronodule with no histological membrane, surrounded by hyperplastic adrenocortex. Together with the three similar ones reported in the literature this case suggests that nodular hyperplasia may be an intermediary stage between diffuse hyperplasia and the appearance of an autonomous adenoma after long-term stimulation of the hyperplastic gland.

Adenoma↗

PubMed1985

Six year remission of ACTH-dependent Cushing's syndrome using bromocriptine.

A patient with ACTH-dependent Cushing's syndrome remained in clinical and biochemical remission six years after pituitary irradiation and while on bromocriptine therapy. When bromocriptine was discontinued urinary free cortisol values became elevated, and were not suppressed by dexamethasone. After reintroduction of the drug, remission was again obtained. It is concluded that bromocriptine is responsible for continuing longterm remission in this case. The possible use of bromocriptine as an adjunctive therapy in ACTH-dependent Cushing's syndrome is discussed.

Adrenocorticotropic Hormone↗

PubMed1981

Plasma prolactin in acromegaly before and after treatment.

Plasma human prolactin (hPRL) was measured in 73 untreated acromegalic patients and was found to be elevated in 32% of the total population. Hyperprolactinemia was present in 40% of the females and in 27% of the male patients. In both groups, plasma hPRL correlated with plasma human growth hormone (hGH) levels with correlation coefficients of 0.38 (P less than 0.05) for females and 0.41 (P less than 0.005) for males. Forty-five patients were treated with conventional supervoltage pituitary irradiation and evaluated 2, 5, and 10 yr after treatment. The patients with hyperprolactinemia before irradiation showed a decrease in plasma hPRL at the most recent follow-up (mean +/- SEM, 125 +/- 34 vs. 67 +/- 15 ng/ml; P less than 0.01), although, in general, they did not achieve normal values. The patients who had normal plasma hPRL before irradiation (mean +/- SEM, 14 +/- 2 ng/ml) had increased levels after therapy (23 +/- ng/ml; P less than 0.005) but remained in the normal range during long term follow-up. In 10 patients followed for 1-10 yr without treatment, there was a tendency for plasma hPRL to rise progressively (mean increment, 122% above the initial value), with individual changes in hPRL strikingly parallel to the changes in plasma hGH. When serum hPRL was initially elevated, similar responses in both hormones were also seen in a small group of patients treated with surgical hypophysectomy. Galactorrhea was present in 5 of the 25 female patients; in 4 of the 5, plasma hPRL was within the normal range. Overall, these data suggest a closer relationship between hGH and hPRL in acromegaly than had been suspected, not only at the level of pituitary secretion but possibly also at the target cell.

Acromegaly↗

PubMed1984

Reduction of follicle-stimulating hormone (FSH) secretion in FSH-producing pituitary adenoma by bromocriptine.

An FSH-secreting pituitary adenoma was demonstrated in a 32-yr-old man who presented with unilateral optic atrophy without any clinical or laboratory evidence of hypogonadism. Semen analysis was normal, although basal FSH levels were markedly elevated (greater than 80 mIU/ml). He had normal plasma LH levels and no other detectable endocrine abnormalities. Administration of GnRH elicited delayed and sustained FSH and brisk LH responses. Administration of TRH resulted in TSH and PRL responses and unexpected FSH and LH elevations. Two surgical operations resulted in temporary reduction of plasma FSH levels, but it increased later concomitant with CT demonstration of tumor growth. After pituitary irradiation, no reduction in FSH levels occurred. A single dose of 5 mg bromocriptine elicited a significant reduction in FSH levels from 137 to 64 mIU/ml. Long term treatment with 15 mg/day bromocriptine resulted in further reduction of FSH level, to 36.4 mIU/ml, without any change in tumor size. This finding implies that bromocriptine could be an adjunctive therapy or an alternative to other modes of treatment in patients with these rare tumors.

Adenoma↗

PubMed2004

Pharmacological therapy for acromegaly: a critical review.

The treatment of acromegaly has changed considerably over the last few decades. In the late 1970s, the introduction of the dopamine receptor agonists made it possible to reduce growth hormone (GH) secretion by somatotropinomas for the first time. Thereafter, the introduction of the somatostatin analogues in the early 1980s had major implications. Recently, the first data on the use of genetically engineered human GH receptor (GHR) antagonists that block GH actions have become available. These GHR antagonists reduce both the biochemical abnormalities of acromegaly, as well as improve clinical signs and symptomatology. In this article we firstly review available data on dopamine agonists. Currently these compounds should be considered in patients with a mixed GH-prolactin secreting pituitary adenoma and/or those in whom pre-treatment insulin-like growth factor (IGF)-I concentrations are below 750 microg/L. We then discuss the somatostatin analogues. These compounds are capable of achieving biochemical control of GH and IGF-I in 50-60% of patients and tumour shrinkage in some 30%. In particular, candidates for treatment with these compounds are those patients who have undergone an unsuccessful transsphenoidal operation or who await the therapeutic effect of external pituitary irradiation. In selected patients primary medical therapy with somatostatin analogues is certainly a feasible option. To date, pegvisomant is the only available member of a new class of drugs that was especially designed to block the GHR. Pegvisomant is the most effective treatment for normalising IGF-I concentrations and appears to have a good safety profile. However, liver function tests should be regularly monitored and tumour size should be closely followed. Finally, we propose a treatment algorithm for acromegaly.

Acromegaly↗

PubMed1992

TSH-secreting pituitary macroadenoma in an 11-year-old girl.

Graves' disease, multinodular toxic goiter or toxic adenoma are the usual causes of hyperthyroidism in children as well as in adults. We report a case of hyperthyroidism due to TSH-secreting pituitary macroadenoma in an 11-year-old girl. The patient was admitted to the Endocrine Department for pituitary function evaluation, five months after transfrontal adenomectomy and pituitary irradiation for a macroadenoma. On admission the patient was clinically hyperthyroid and the work-up established a diagnosis of hyperthyroidism due to TSH-secreting adenoma (high levels of TSH in the face of hyperthyroidism, no TSH response to TRH stimulation, diffuse thyroid goiter without eye signs or pretibial myxedema). Of interest in this case was the fact that: (a) she is the youngest patient reported with hyperthyroidism due to a TSH-secreting macroadenoma and (b) hyperthyroidism was diagnosed after adenomectomy.

Adenoma↗

PubMed1977

Interstitial gamma irradiation by 198Au of the pituitary in diabetic retinopathy. Selective growth hormone blockade and ocular results.

Pituitary interstitial irradiation by stereotaxic implantation of a gamma pointemitter was performed in 110 patients with progressing diabetic retinopathy. Reduction of growth hormone secretion peaks was delayed, but was consistent and selective in all cases controlled by somatotropin stimulation test, while other pituitary secretions remianed unchanged in all but five cases. In 31 patients who had no associated photocoagulation, long-term postoperative assessment showed significant improvement of hemorrhages and intrarentinal new vessels with preservation of visual acuity. Preretinal vascular proliferation (except when treatable by photocoagulation), extensive retinitis proliferans, and macular deterioration are contraindications. This technique represents a new approach in the functional pituitary neurosurgical treatment of diabetic retinopathy and differs from all other procedures that result in a more or less complete hypophysectomy.

Body Weight↗

PubMed1990

[Clinical and histological study of pituitary fibrosarcoma following radiotherapy for pituitary adenoma. Case report].

A 49-year-old male was admitted with a history of radiotherapy for a pituitary adenoma 9 years earlier. Three weeks prior to admission, he noticed visual loss in the left eye. Computed tomography (CT) scan revealed a sellar tumor. The patient underwent craniotomy and the tumor was partially resected. The histological diagnosis was benign pituitary adenoma. Two months after surgery, he began to complain of headache and left hemiparesis. CT scan at that time showed a large parasellar tumor extending into the right temporal lobe. A second craniotomy was performed and a firm tumor was partially removed. Under light microscopy, the tumor was composed of anaplastic spindle cells showing a fascicular pattern. Ultrastructurally, the tumor cells were spindle-shaped with elongated nuclei. The cytoplasm contained numerous distended rough endoplasmic reticula and free ribosomes, Golgi apparatus as well as glycogen granules. Some desmosome-like intercellular adherent were observed. Collagen fibers were scattered in the extracellular space. There was no apparent formation of a basement membrane. These findings suggested a close morphological similarity between tumor cells and fibroblasts, conforming to ultrastructural diagnostic criteria for fibrosarcoma. In spite of intensive treatment, such as a second radiotherapy and subsequent craniotomy, the patient died 9 months after admission. The clinical course and pathological findings of the post-irradiation pituitary fibrosarcoma are discussed.

Adenoma↗

PubMed2006

Medical treatment of acromegaly: comorbidities and their reversibility by somatostatin analogs.

Relief of symptoms can be achieved following surgery for growth hormone (GH)-secreting adenomas, as well as after pharmacological therapy with somatostatin analogs. Recently, long-acting somatostatin analog depot formulations, octreotide LAR and lanreotide SR have become available. Somatostatin analogs control GH/insulin-like growth factor (IGF)-1 excess, induce tumor shrinkage in a high proportion of patients, improve symptoms of acromegaly with relatively limited side effects and are successfully administered in patients not suitable for surgery. Furthermore, preoperative somatostatin analogs have been suggested to improve outcome for tumors with limited invasiveness, while surgical tumor debulking in cases that are, at least partially, somatostatin resistant, increases the achievement of normal IGF-1 levels by postoperative somatostatin analog treatment. Effective control of hypertension, as well as diabetes, is mandatory in order to reduce the increased vascular morbidity/mortality. Control of GH/IGF-1 excess generally improves glucose metabolism. Somatostatin analogs improve insulin sensitivity, exerting, however, a concomitant direct inhibitory effect on insulin secretion, with a net balance leaning towards a deterioration in glucose homeostasis. As a result, oral insulin secretagogues (and/or insulin) should probably be preferred to insulin sensitizers in acromegalic patients developing diabetes while on somatostatin analogs. Nevertheless, glucose tolerance remains normal in most of the nondiabetic acromegalic patients, while diabetic acromegalic patients on insulin are at risk for hypoglycemia during initiation of somatostatin analog therapy. Although successful management of acromegaly has been associated with improvement in morphological and functional parameters of cardiomyopathy, limited and conflicting information is available regarding the effect on blood pressure control. Contradictory results have also been reported regarding sleep hypopnea or apnea in treated acromegalic patients. As acromegalic skeletal abnormalities are rather irreversible, apneic episodes may persist after normalization of hormonal levels. Aggressive therapy, including surgery, pharmacological treatment and, in some cases, pituitary irradiation, aiming at normalization of IGF-1 levels, is required for arthropathy management. Some improvement in pain, crepitus and range of motion has been observed after treatment with somatostatin analogs. Information on the impact of disease control, either by surgery or somatostatin analog treatment, on gonadal function is limited. Finally, the link between the hormonal/biochemical and the psychiatric/psychological features of acromegaly, as well as a potential basis for positive effects of somatostatin analog therapy remain unclear.

Acromegaly↗

PubMed1985

[Clinical analysis of large and/or invasive pituitary adenomas].

To establish a more reasonable therapeutic guide line for large and/or invasive pituitary adenomas, 257 cases of pituitary adenoma were analyzed. Among 83 cases with slight or moderate suprasellar extension (Wilson's Grade II-A & B) in the pre-CT era, 57 patients were alive at the time of follow-up (mean follow-up period: 12.7 years). Death of unspecified causes other than cancer, myocardial infarction, etc. were reported in nine patients. Among 60 cases of Grade II-A & B in the post-CT era, 59 patients were alive (mean follow-up: 3.4 years). Comparing these groups, cases with huge suprasellar extension (Grade C) had much worse prognosis. Only two patients were alive among 14 cases of Group C in the pre-CT era. Seven cases of death with unspecified causes were reported. In the 13 cases of Group C in the post-CT era, 12 patients were alive but at least four of them were severely handicapped. In 10 cases with sphenoid invasion (Grade IV) in the pre-CT era, only two were alive. In the group of Grade IV in the post-CT era, one patient died and three patients were operated repeatedly. Severe complications of irradiation therapy occurred in seven patients (mean interval: 6.6 years) among 120 cases of irradiated pituitary adenomas in every category. Among six cases with histological malignancy, three were operated repeatedly; among the latter group, two patients died and the third showed intracranial metastases. The present data indicate that large and/or invasive pituitary adenomas have a pessimistic prognosis, although adenomas with mild or moderate simple suprasellar extension have fairly good prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

PubMed2005

Bone mineral density at diagnosis and following successful treatment of pediatric Cushing's disease.

Bone mineral density (BMD) is frequently reduced in children and adolescents with Cushing's disease (CD), but there is little follow-up data after cure. BMD was determined by dual energy X-ray absorptiometry (DEXA) in two groups of patients with CD. Group 1 comprised 8 patients, 5 males and 3 females, aged 12.4 yr (8.2-16.8), assessed at diagnosis. Group 2 comprised 11 subjects, 6 males and 5 females, diagnosed at age 13.3 yr (6.4-17.4), cured by transsphenoidal surgery (TSS) (no.=7) or TSS + pituitary irradiation (no.=4). They had measurement of BMD, at mean age of 18.3 yr (11.1-28.5), i.e. 4.5 yr (0.8-11.4) after cure. Four patients, mean age 20.2 yr (17.6-22.4), had repeated DEXA'scans, 1-4 times, for up to 5.8 yr. After cure, GH deficiency was present in 9 patients and treated with hGH in 8. In Group 1, patients' L2-L4 volumetric (v)BMD Z-score was variable with a mean of -1.04 (-3.21-0.11). L2-L4 vBMD Z-score values correlated negatively with midnight cortisol (p < 0.05). In Group 2, mean L2-L4 vBMD was -0.38 (-1.0-0.13); and in 7/11, mean femoral neck (FN) areal (a)BMD Z-score was 0.14 (-1.62-2.46). FN aBMD Z-score was higher than L2-L4 aBMD Z-score (p < 0.05). In patients with repeated scans, mean change in L2-L4 vBMD Z-score was 0.20 (-0.15-0.45), and mean change in FN aBMD Z-score 0.03 (-0.53-0.38). These findings show variability of BMD at diagnosis and near normal BMD after cure of pediatric CD, suggesting that with appropriate replacement of pituitary hormone deficiency normal peak bone mass is achievable.

Absorptiometry, Photon↗

PubMed1981

Hypersecretion of an abnormal form of follicle-stimulating hormone associated with suppressed luteinizing hormone secretion in a woman with a pituitary adenoma.

Pituitary tumors producing FSH have hitherto been reported only in males, all of whom have had normal or raised LH levels in serum. This report describes a female with a pituitary adenoma associated with supranormal serum levels of FSH. The FSH was also qualitatively abnormal when compared with FSH in the serum of other postmenopausal women, had a lower apparent molecular weight on gel chromatography, and was less negatively charged, as shown by electrophoresis. The results of LRH tests and suppression tests with ethinyl estradiol indicated autonomy of the FSH-producing adenoma. The FSH level increased concomitant with tumor enlargement and decreased after surgical removal of the pituitary adenoma or pituitary irradiation. The serum level of the glycoprotein alpha-subunit was raised about 100-fold. Any free FSH beta-subunits were not detectable in serum. The abnormal FSH had antigenic sites in common with both the alpha- and beta-subunits of FSH. The LH level was extremely low, and there was no response to LRH tests or ethinyl estradiol treatment. After gel chromatography, a small amount of LH, corresponding to 1/50th of the average for the patient's age, was detected at the position for normal LH. There was no GH response to insulin-induced hypoglycemia, while the cortisol increase was normal. Thyroid and adrenal functions were normal. The PRL level was within the normal range and increased slightly after estrogen treatment.

Adenoma↗

PubMed2006

A follow-up of 130 patients with acromegaly in a single centre.

OBJECTIVES: Acromegaly is a rare disease with increased mortality rate. The aim was to present our centre experience in the diagnosis and treatment of a series of patients suffering from acromegaly. METHODS: 130 patients (55 men, 75 women) aged 19-84 years presenting with clinical and hormonal features of acromegaly, attending Department of Endocrinology and Out-patient Clinic between 1990 and 2004 were studied. They were analyzed their GH and IGF-1 levels, CT and MRI scans, and they were administered medical therapy, neurosurgery and radiotherapy. RESULTS: We have observed 106 macro-, 16 microadenomas and 1 case of ectopic GHRH. 115 patients were operated, as cured were recognized 74 of them. Pituitary irradiation was applied to 11 patients, in 4 of them it did not cure the disease. Medical therapy was efficacious in 12% patients treated with bromocriptine, 73% with long-acting lanreotide and 58% with long-acting octreotide. In 7 patients other malignant neoplasm were detected. 11 patients died during the follow-up. CONCLUSIONS: There is possible underdiagnosis of acromegaly in our region, especially in males. We have observed better diagnostic opportunities in recent years when MRI was available. It was accompanied by better outcome of surgical and pharmacological treatment and better control of the complications of the disease.

Acromegaly↗