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PubMed1978

[Multiple recurrence of Cushing's syndrome after bilateral adrenalectomy and pituitary gland surgery. Cure with o,p'-DDD].

A pituitary-dependent Cushing's syndrome in a young woman had an unusually protracted course and was extremely resistant to therapy. After unsuccessful pituitary irradiation, bilateral total adrenalectomy was performed. A piece of an excised adrenal gland was reimplanted into a buttock. Nevertheless, the patient went into adrenocortical failure and had to be given replacement therapy. After three years the Cushing's syndrome reappeared, this time combined with general hyperpigmentation. The implanted adrenal tissue was no longer to be found. Neither stereotactic pituitary coagulation nor implantation of 90-Yttrium into the pituitary resulted in remission of Cushing's syndrome. All attempts to localize the--very probably ectopic--cortisol-producing adrenocortical tissue failed. However, complete remission was finally achieved by treatment with o,p'-DDD.

Adolescent↗

PubMed1999

Diagnosis and management of Cushing's syndrome: results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis.

The past 45 yr' experience with Cushing's syndrome (CS) has led to the awareness of its complex nature and, by the same token, brought about an increase in the diagnostic and therapeutic dilemmas. We carried out a retrospective multicentre study on the diagnostic work-up and treatment in 426 patients with CS, subdivided as follows: 288 with Cushing's disease (CD), 80 with an adrenal adenoma, 24 with an adrenal carcinoma, 25 with ectopic ACTH and/or CRH secretion, and 9 with ACTH-independent nodular adrenal hyperplasia. Normal urinary free cortisol (UFC) values among multiple collections were recorded in about 10% of patients with CS. In 28% of patients with ACTH-independent CS, basal ACTH concentrations were within the normal range but did not respond to CRH stimulation. Measurement of ACTH levels by immunoradiometric assay, rather than by RIA, offered a greater chance of recognizing patients with ACTH-independent CS or ectopic secretion. A 50% increase in ACTH or cortisol levels after CRH yielded a diagnostic accuracy of 86% and 61%, respectively, in the differential diagnosis of ACTH-dependent CS. An 80% decrease in cortisol levels after 8 mg dexamethasone overnight, or in UFC values after the classical 2-day administration, excluded an ectopic secretion but carried a low negative predictive value given the high number of nonsuppressors among patients with CD. Pituitary imaging identified an adenoma in 61% of patients with CD. At inferior petrosal sinus sampling, an ACTH centre: periphery gradient after CRH less than 3, correctly classified all patients with ectopic secretion but misdiagnosed 15% of 76 patients with CD. Transsphenoidal pituitary surgery, the standard therapy for CD, resulted in complete remission (appearance of clinical signs of adrenal insufficiency associated with low/normal UFC excretion and, when available, low/normal morning plasma ACTH and cortisol levels) in 69% of patients. The overall relapse rate after pituitary surgery was 17%. The probability of relapse-free survival, as assessed by Kaplan-Meier analysis, was 95% at 12 months, 84% at 2 yr, and 80% at 3 yr. Risk of relapse was significantly correlated with postoperative baseline plasma ACTH and cortisol peak after CRH. No relapses were observed among patients who did not respond to CRH. Other therapeutic approaches for CD, such as pituitary irradiation and medical therapy, resulted in normalization of cortisol secretion in about half of treated cases. In summary, an accurate selection of the available diagnostic tools leads to the correct diagnosis in the majority of patients with CS. The therapeutic options for CD, adrenal carcinoma, and ectopic secretion are, as yet, not fully satisfactory. The high incidence of relapse after pituitary surgery calls for a prolonged follow-up.

Adenoma↗

PubMed1981

Pure alpha-secreting pituitary adenomas.

Isolated hypersecretion of the alpha subunit of the glycoprotein hormones occurred in two men with previously diagnosed "nonfunctioning chromophobe adenomas." The alpha hypersecretion was unresponsive to hypothalamic releasing hormone, thyroid hormone, and sex-steroid hormones. After trans-sphenoidal surgery and conventional pituitary irradiation, alpha secretion was decreased. Increased quantities of immunologically active and biologically inactive luteinizing hormone (LH) material were detected in serum and in tumor homogenate. Immunologic and gel-chromatographic studies determined that only the alpha subunit was present and that it was cross-reacting in the LH immunoassay. These studies suggest that the alpha subunit may be a useful marker of pituitary tumors, particularly in patients without clinical evidence of hormonal hypersecretion.

Adenoma, Chromophobe↗

PubMed2003

Sustained improvement in vision in a recurrent growth hormone secreting macroadenoma during treatment with octreotide in the absence of marked tumour shrinkage.

Visual improvement following octreotide for growth hormone secreting pituitary macroadenomas is uncommon without tumour shrinkage. A 45-year old lady presented with blurred vision for 12 months. Visual assessment revealed a bitemporal hemianopia and CT scan demonstrated a large pituitary tumour with lateral and suprasellar extension. Acromegaly was confirmed by 75 g glucose tolerance testing. Primary transsphenoidal surgery was performed with normalisation of visual acuity and fields of vision. Post-operatively she had anterior pituitary hormone deficiency. As GH and IGF-1 levels remained elevated she underwent external pituitary irradiation. CT scanning demonstrated tumour shrinkage associated with a modest fall in GH levels. IGF-1 levels remained elevated falling to the age-related upper limit of normal after 5 years. At regular review she had stable visual acuity and fields of vision. She presented as an emergency 7 years from presentation with reduced vision and recurrence of bitemporal hemianopia. An MRI demonstrated a large pituitary adenoma. We therefore undertook a carefully monitored trial of octreotide with great caution with daily reassessment of acuity and fields. A decision was made to proceed to surgery in the event of deterioration or lack of improvement after a short trial over 5-7 days. We observed normalisation of visual acuity and perimetry within 3 days. She then commenced long-acting octreotide (Sandostatin LAR) 20 mg every 28 days. MRI after 1 week showed shrinkage of the tumour by a few millimetres. Five months later repeat MRI failed to show any further improvement in tumour size. However she remains well 29 months from treatment with normal vision and is being monitored carefully as her chosen form of therapy. Somatostatin analogues may be effective as therapy in a selected group of patients with acromegaly and visual loss who are not suitable for pituitary surgery. If used in this way the drug must be given cautiously with frequent detailed ongoing visual assessments. In this present case there has been a restoration of vision but the long-term outlook remains guarded without significant tumor shrinkage.

Adenoma↗

PubMed1989

Prolactin and luteinizing hormone profiles of cured acromegalic subjects.

The 24-h PRL and LH hormone profiles were analysed of 16 cured male acromegalic patients who had undergone selective transsphenoidal surgery 4-9 years previously. Eight of these patients also underwent pituitary irradiation. Blood samples were taken at 20-min intervals; the PRL and LH data were analysed with the cluster program. ARIMA modelling, cross-correlation techniques, Fourier analysis, and cosinor analysis. About 10-11 PRL and LH peaks were demonstrated for both non-irradiated and irradiated patients. The absolute heights of PRL pulses and the mean valley levels were significantly greater for irradiated patients than for non-irradiated patients, but the increment in amplitude did not differ. A significant diurnal rhythm for PRL was found for all non-irradiated patients but for only one irradiated patient. LH pulse area and amplitude were lower in the group of irradiated patients. The incremental responses of LH and PRL to GnRH and TRH, respectively, were lower in irradiated patients than in non-irradiated patients. During the night (0200-0800 h) the number of PRL pulses decreased in non-irradiated patients but not in irradiated patients. Pulse nadirs and amplitudes increased during the evening and night in non-irradiated patients but were constant in irradiated subjects. Bivariate modelling of the data for 14 patients revealed significant cross-correlations between LH and PRL pulses in nine subjects. This study demonstrates that the pulsatile secretion of PRL and LH in treated acromegalics is basically normal. Additional radiation therapy, however, may lead to damage of the hypothalamus, as reflected by the absence of a circadian PRL rhythm. A direct influence on the pituitary by radiation is indicated by the decreased magnitude of LH pulses and the diminished response of LH and PRL after injection of GnRH and TRH, respectively.

Acromegaly↗

PubMed1977

Transient bitemporal hemianopsia during pregnancy after treatment of galactorrhea-amenorrhea syndrome with bromocriptine.

A patient is described with a galactorrhea-amenorrhea syndrome and an enlargement of the sella turcica. Pregnancy occurred after induction of ovulation with bromocriptine (and 2.5 years after pituitary irradiation). Periodic assessment of the visual fields showed an increase in size of the blind spots after 10 weeks and a moderate bitemporal hemianopsia after 22 weeks, which improved spontaneously after 30 weeks of pregnancy. One month after delivery the visual field of the left eye was almost normalized, while that of the right eye showed a definite improvement. Prior radiotherapy need not prevent visual complications from enlargement of pituitary adenomas during pregnancy.

Adult↗

PubMed1978

Pregnancy in a case of Nelson's syndrome.

A woman suffering from Cushing's disease from the age of 17 who had been treated consecutively with pituitary irradiation, bilateral partial adrenalectomy and o,p'-DDD (Mitotane, USP) presented the clinical picture of Nelson's syndrome (hypoadrenalism with secondary hypersecretion of ACTH and MSH) at the age of 32. Under substitution therapy with corticoids she became pregnant for the first time at the age of 38. The course of the pregnancy was normal and at term she was delivered of a normal child by Cesarean section. The materno-fetal relationship, the increased risk of pituitary infarction during pregnancy and the possible teratogenic effect of chemotherapy in such cases are discussed.

Adrenal Cortex Hormones↗

PubMed1992

Intracranial and intraspinal dissemination of an ACTH-secreting pituitary tumor.

A case of a 29-year-old man with an ACTH-producing pituitary tumor disseminated into the subarachnoid space is described. After total adrenalectomy for Cushing's disease at the age of 15, Nelson's syndrome developed. Transsphenoidal adenomectomy at 17 and 21 years of age, pituitary irradiation and medical therapies with sodium valproate, baclofen and bromocriptine failed to lower his plasma ACTH level. Multiple intracranial and intraspinal tumors associated with the symptoms of left hemiparesis developed. The removal of a tumor grown at the level of C1-3 was performed with successful palliation of his symptoms. Histologically, the tumor cells showed sinusoidal, papillary and diffuse patterns with a preponderance of the former over the latter two, although the papillary pattern predominated in the primary pituitary tumor. Immunohistochemical analysis demonstrated most cells to be positive for ACTH in the metastatic tumor as well as the primary adenoma. The clinical significance of his course is discussed with a review of 11 reported cases with metastatic ACTH-producing pituitary tumors.

Adrenocorticotropic Hormone↗

PubMed1984

[Surgery in endocrine disorders. 1. Pituitary tumors].

Microsurgical refinement of classical transsphenoidal pituitary surgery facilitated selective adenomectomy with preservation of normal residual pituitary, thus becoming the first choice in the management of functioning pituitary adenomas. However, lack of tumor capsule and invasive nature of the adenoma make its total removal still difficult. Peritumoral wedge resection is most recommended from our experiences. Surgical results of acromegaly have become quite satisfactory and normal postoperative serum GH levels have been obtained in nearly 100% of the cases with micro or enclosed-adenoma. Pituitary irradiation and/or bromocriptine therapy are, however, yet necessary in half of the cases with marked suprasellar extension or invasion into the surrounding tissues. In the management of macroprolactinoma, surgical excision should precede bromocriptine therapy, because fibrous changes of the adenoma caused by the drug make surgical intervention much difficult. Microprolactinoma can be treated satisfactorily either by surgery or by bromocriptine. Just follow-up observation may be indicated to the cases having no hope for baby. All impaired pituitary functions in Cushing's disease can be converted normal by selective adenomectomy. However, highly qualified microsurgical technique and systematical survey for microadenoma are mandatory, otherwise it is often elusive.

Acromegaly↗

PubMed1998

Short-term endocrinological results after gamma knife surgery of pituitary adenomas.

We report our preliminary results after the radiosurgical treatment of 25 secreting pituitary adenomas with a mean follow-up of 20 months (range 6-36 months). Fifteen acromegalic patients showed a decrease of 65% in mean growth hormone (GH) levels after 6 months and of 77% after 12 months. Only 3 patients (20%) are considered to be in remission (mean GH and IGF1 level into the normal range). A decrease of prolactin (PRL) was noted in 46% and 64% at 6 and 12 months after radiosurgery in 4 patients with prolactinomas. There was no case of PRL normalizaion. At present 3/4 patients have individual PRL levels slightly above the normal range. A normalization of Urinary Free Cortisol (UFC) was noticed in 4/6 (66%) patients Cushing's disease within 6-12 months. Pituitary deficiency was noticed in this series in 4/25 patients (16%) who received subtotal or total pituitary irradiation for large postoperative remnants of secreting adenomas poorly defined on magnetic resonance imaging (MRI).

Acromegaly↗

PubMed1988

Acromegaly from ectopic growth hormone-releasing hormone secretion by a malignant carcinoid tumor. Successful treatment with long-acting somatostatin analogue SMS 201-995.

A 26-year-old man with acromegaly secondary to ectopic growth hormone-releasing hormone (GHRH) secretion by a metastatic carcinoid tumor is the subject of this study. He previously failed to respond to conventional therapeutic modalities (partial hypophysectomy, pituitary irradiation, high-dose bromocriptine and a combination of streptozotocin and 5-fluorouracil) and was treated with long-acting somatostatin analogue SMS 201-995 (Sandoz, East Hanover, NJ). Growth hormone and somatomedin C concentrations became normal, and GHRH-LI (GHRH-like immunoreactivity) was suppressed by more than 60%. The growth hormone response to exogenous GHRH 1-40 was stopped and growth hormone rise to thyrotropin-releasing hormone (TRH) was significantly attenuated. A significant shrinkage of the pituitary gland was observed. Similarly, the size of the metastatic carcinoid lesions decreased dramatically and was accompanied by a normalization of liver function. After almost 2 years of SMS 201-995 therapy, the patient was well and had no clinical signs of acromegaly. Thus, SMS 201-995 appears to be a remarkably effective agent for treatment of acromegaly secondary to ectopic GHRH secretion.

Acromegaly↗

PubMed1984

Concomitant falls of plasma cortisol and ACTH levels in a case of Cushing's disease during treatment with trilostane.

A 72-year-old man with Cushing's disease was treated with trilostane, a competitive inhibitor of adrenal 3 beta-hydroxysteroid dehydrogenase (3 beta-HSDH). The treatment with trilostane successfully lowered urinary excretion of 17-hydroxycorticosteroids (17-OHCS) and plasma levels of cortisol and elevated the plasma level of dehydroepiandrosterone. Unexpectedly, plasma ACTH fell from 109.7 +/- 45.0 to 42.7 +/- 27.3 pg/ml (P less than 0.01) in parallel with plasma cortisol. The hyperresponsiveness of plasma ACTH observed both in the metyrapone test and the lysine-vasopressin test was also ameliorated by treatment with trilostane. Then low dose of pituitary irradiation with cobalt-60 was added and his urinary excretion of 17-OHCS and plasma levels of cortisol decreased further. After treatment with trilostane was finally stopped, the plasma ACTH increased from 45.9 +/- 21.9 to 69.6 +/- 25.3 pg/ml (P less than 0.05) in parallel with plasma cortisol. Since then he has had no recurrence for 12 months. These observations suggest that trilostane, like other adrenal enzyme-inhibiting drugs, may induce unexpected improvement of the abnormality of the hypothalamic-pituitary axis present in Cushing's disease.

17-Hydroxycorticosteroids↗

PubMed1983

Sodium valproate and cyproheptadine may independently induce a remission in the same patient with Cushing's disease.

A patient with Cushing's disease was unsuccessfully treated by pituitary surgery and external pituitary irradiation. One year later sodium valproate treatment induced a remission and finally hypocorticism developed. After drug withdrawal hypercoticism recurred. Treatment with cyproheptadine again induced hypocorticism necessitating corticosteroid substitution therapy. Biochemical characteristics of this patient included responsiveness to bromocriptine and cyproheptadine in acute tests. The study demonstrates that sodium valproate and cyproheptadine may both be effective independently in the treatment of the same patient with Cushing's disease. It is proposed that the disease is due to an ACTH producing tumour of pituitary intermediate lobe origin.

Adrenocorticotropic Hormone↗

PubMed1988

Transsphenoidal microsurgery as primary treatment in 25 acromegalic patients: results and follow-up.

Twenty-five patients with acromegaly were treated by transsphenoidal microsurgery. Fourteen patients (56%) were considered cured according to the following criteria: a. basal plasma GH less than 10 mU/l; b. glucose suppressed plasma GH less than or equal to 4 mU/l, and c. disappearance of TRH responsiveness if present preoperatively. Thirteen of the cured patients were re-evaluated after a mean follow-up period of 3.5 years (range 1.5 to 5.5 years). At that time, basal plasma GH was still less than 10 mU/l and glucose suppressed plasma GH was still less than or equal to 4 mU/l in all patients, indicating the practical value of our criteria. The remaining 11 patients (44%) received additional treatment by external pituitary irradiation and bromocriptine. Owing to surgery, 5 patients (20%) developed partial or panhypopituitarism.

Acromegaly↗

PubMed2001

Experience with pegvisomant in the treatment of acromegaly.

Established modalities of therapy for acromegaly (surgical adenomectomy, external beam pituitary irradiation, oral dopamine agonists, and injectable somatostatin analogues) have as their common goal the lowering of circulating growth hormone (GH) levels, with a consequent reduction in serum insulin-like growth factor I (IGF-I). Pegvisomant is a GH receptor antagonist that inhibits GH receptor dimerization and has a powerful ability to lower serum IGF-I levels in patients with active acromegaly. Currently available data suggest that pegvisomant is an effective treatment for acromegaly that is safe, well tolerated, and not associated with expansion of residual pituitary tumour over the time period studied.

Acromegaly↗

PubMed2001

Autoimmune hypothyroidism coexisting with a pituitary adenoma secreting thyroid-stimulating hormone, prolactin and alpha-subunit.

A 44-year-old woman presented to her GP with excessive tiredness. She had positive thyroid microsomal and thyroglobulin autoantibodies and was found to have an elevated serum thyroid-stimulating hormone (TSH) concentration of 8.37 (normal = 0.15-3.5)mU/L and a low normal total thyroxine (T4) of 86 (reference range 60-145)nmol/L. She was rendered symptom free on a dose of 150 microg of thyroxine per day. However, her TSH failed to return to normal, and following a further increase in her thyroxine dose she was referred to the endocrine clinic for further assessment. Her TSH at this stage was 14mU/L, free T4 (fT4) 28 (normal = 10-27)pmol/L and free T3 (fF3) 10 (normal = 4.3-7.6)pmol/L. She denied any problems with adherence to her medication. Her serum prolactin was elevated at 861 (normal = 60-390)mU/L. A pituitary tumour was suspected and an MRI scan showed a macroadenoma of the right lobe of the pituitary, extending into the suprasellar cistern. The tumour was resected trans-sphenoidally. Electron microscopy showed a dual population of neoplastic cells compatible with a thyrotroph cell and prolactin-secreting adenoma. Immunocytochemistry and cell culture studies confirmed the secretion of TSH, prolactin and alpha-subunit. Postoperative combined anterior pituitary function tests did not demonstrate any deficiency of anterior pituitary hormones. A repeat MRI scan showed no significant residual tumour; however, her serum TSH and prolactin levels remained high and she was given a course of pituitary irradiation. This case illustrates the difficulty of diagnosing a TSHoma when it coexists with autoimmune hypothyroidism. We believe the combination of pathologies reported here is unique.

Adrenocorticotropic Hormone↗

PubMed2000

Long-term follow-up results of postoperative radiotherapy in 36 patients with acromegaly.

In acromegaly, pituitary irradiation is a slow, but effective, intervention in decreasing GH concentration. Few studies addressing the outcome of radiotherapy have used the currently accepted strict criteria for remission in the analysis of data. These studies report a low percentage of remission after radiotherapy. Doubt has especially been raised as to whether radiotherapy is effective in normalizing serum insulin-like growth factor (IGF)-I concentration. We analyzed the long-term follow-up data of postoperatively administered radiotherapy in 36 patients with postoperative persistent acromegaly, using both the normalization of GH suppression during oral glucose loading (GTT) and the normalization of IGF-I concentration as criteria for remission. Before radiotherapy, mean suppressed GH was 9.8 +/- 1.9 mU/L (n = 31), and mean IGF-I concentration was 44.3 +/- 3.9 nmol/L, equivalent to + 4.76 +/- 0.78 age-related IGF-I SD score (n = 13). The median radiation dose was 40 Gray (range, 25-50 Gray). At 5, 10, and 15 yr follow-up, 18 out of 30 patients (60%), 23 out of 31 patients (74%), and 16 out of 19 patients (84%), respectively, achieved normal serum IGF-I concentration. At the last assessment of all patients, after a mean follow-up period of 139 +/- 12 months, 27 out of 36 (75%) patients had a normal IGF-I concentration without additional medication, whereas 5 patients still required treatment with octreotide. Remission, as judged by normalization of GH suppression during GTT, was documented in 65% of patients from 2-5 yr after radiotherapy (n = 34); in 69% of patients, up to 10 yr after radiotherapy (n = 29); and in 71% of patients, up to 15 yr post irradiation (n = 17). At the latest assessment, a mean of 125 +/- 11 months after radiotherapy, 71% of patients (n = 35) were in remission, as defined by normal suppression of serum GH during GTT. Remission, as judged by normalization of both GTT and IGF-I, was found in 40% of patients 3-5 yr after radiotherapy (n = 30); in 61% of patients, 6-10 yr after radiotherapy (n = 28); in 65%, after 11-15 yr after radiotherapy (n = 17); and in 63% of patients, at the end of the follow-up period (n = 35). Substitution of one or more pituitary hormone deficiencies was required in 11% of patients postoperatively; in 29%, 5 yr after radiotherapy; in 54%, 10 yr after radiotherapy; and in 58%, more than 15 yr after radiotherapy. Our findings support the use of radiotherapy as an effective intervention in the treatment of residual clinical activity of disease after surgery for acromegaly.

Acromegaly↗

PubMed2002

[Experience in treating acromegalic patients with long-acting octreotide].

The authors report clinical observations in 12 acromegalic patients treated with long-acting octreotide (Sandostatin LAR, Novartis, 20 mg intramuscular injection per 28 days administered for 6-36 months). Clinically and hormonally active acromegaly was evidenced in all patients by the presence of typical clinical symptoms, increased serum growth hormone and insulin-like growth factor I concentrations, and by non-suppressible serum growth hormone levels after oral glucose administration. In all patients previous treatments (transsphenoidal surgery, pituitary irradiation and bromocriptine therapy) were uneffective or contraindicated, or they were refused by the patients. Octreotide test (Sandostatin, Novartis, 100 g subcutaneously) performed in all patients before treatment precisely predicted the hormonal effectiveness of long-acting octreotide treatment. Three-six months after therapy serum growth hormone levels decreased from 13.6 +/- 3.9 ng/ml (mean +/- SD) to 3.4 +/- 1.7 ng/ml, while insulin-like growth factor I concentrations decreased from 483 +/- 127 ng/ml to 248 +/- ng/ml. Of the 12 patients 7 (58%) had serum growth hormone levels considered as safe values (< 2.5 ng/ml), whereas in 9 patients (75%) serum insulin-like growth factor I concentrations returned to age- and sex-matched normals. Repeat pituitary magnetic resonance imaging performed in 8 patients treated longer than 1 year revealed a decrease of tumor size in 3 patients (37%). There was a considerable clinical improvement during treatment: severe headache, which was present in most patients, as well as perspiration, joint pain, swelling of extremities, and weakness markedly decreased or disappeared. These results indicate that long-acting octreotide offers a very effective treatment of choice in acromegalic patients in whom other previous therapies were ineffective, contraindicated, or refused.

Acromegaly↗