Ectopic pituitary adenoma of the clivus presenting with apoplexy: case report and review of the literature

Ectopic pituitary adenomas usually occur within sphenoid sinus or nasopharynx, and seldom within the clivus. There is only a single reported example of ectopic adenoma with clinical apoplexy, albeit not from clivus. We report a 78-year-old male with known prostate carcinoma admitted with acute onset of blurred vision, suggestive of apoplexy. Work-up revealed unilateral cranial nerve VI palsy and neuroimaging showed a mass confined to the clivus; sellar region was normal. Preoperative considerations included chordoma, chondrosarcoma, or metastatic prostate carcinoma to bone. Resection was via endoscopic transsphenoidal approach to the clivus. An ectopic null cell pituitary adenoma with bland infarction was identified as the cause of the patient's clinical apoplexy. No antecedent precipitating factors for apoplexy were present; specifically the patient had not received leuprolide preoperatively, a known precipitant of pituitary apoplexy in prostate cancer patients who receive drug. We review the literature on ectopic clival pituitary adenomas, apoplexy in ectopic adenomas, and the link between apoplexy and leuprolide usage.     

Pituitary hyperplasia after goserelin (LHRH–analogue) therapy

A 78-year-old male was treated with goserelin (Zoladex) for 16 months for metastasizing prostate carcinoma. This therapy is clinically equivalent to orchidectomy, as the application of the luteinizing hormone-releasing hormone (LHRH)-analogue Zoladex causes suppression of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by down-regulation of pituitary receptors. Consequently, testicular androgen production is inhibited and testosterone levels are decreased to castration levels. In the present case we found diffuse, partially nodular hyperplasia of growth hormone (GH) and adrenocorticotropin (ACTH) producing cells in the anterior pituitary gland at autopsy. As Zoladex reduces pituitary receptors for releasing hormones (RH), a globally increased hypothalamic secretion of RH might be responsible for the ACTH- and the GH-cell hyperplasia. We cannot exclude that Zoladex may cause not only adenomas in rat pituitary glands as reported previously, but also a (nodular) hyperplasia of the pituitary gland in man.     

Pituitary apoplexy in a child presenting with massive subarachnoid and intraventricular hemorrhage.

A case of pituitary apoplexy in a child with massive subarachnoid and intraventricular hemorrhage is reported. The patient presented with a sudden onset of headache, diminution of visual acuity and a bitemporal visual field defect. Computerized tomography revealed a massive subarachnoid hemorrhage with extension of blood into the third ventricle. Angiography did not show an aneurysm. The patient was operated on and altered blood within a necrotic pituitary adenoma was decompressed. His vision and field defect improved along with resolution of headache in the postoperative period.     

High‐Cholesterol Diet Disrupts the Levels of Hormones Derived from Anterior Pituitary Basophilic Cells

Emerging evidence shows that elevated cholesterol levels are detrimental to health. However, it is unclear whether there is an association between cholesterol and the pituitary. We investigated the effects of a high‐cholesterol diet on pituitary hormones using in vivo animal studies and an epidemiological study. In the animal experiments, rats were fed a high‐cholesterol or control diet for 28 weeks. In rats fed the high‐cholesterol diet, serum levels of thyroid‐stimulating hormone (TSH; also known as thyrotrophin), luteinising hormone (LH) and follicle‐stimulating hormone (FSH) produced by the basophilic cells of the anterior pituitary were elevated in a time‐dependent manner. Among these hormones, TSH was the first to undergo a significant change, whereas adrenocorticotrophic hormone (ACTH), another hormone produced by basophilic cells, was not changed significantly. As the duration of cholesterol feeding increased, cholesterol deposition increased gradually in the pituitary. Histologically, basophilic cells, and especially thyrotrophs and gonadotrophs, showed an obvious increase in cell area, as well as a potential increase in their proportion of total pituitary cells. Expression of the β‐subunit of TSH, FSH and LH, which controls hormone specificity and activity, exhibited a corresponding increase. In the epidemiological study, we found a similar elevation of serum TSH, LH and FSH and a decrease in ACTH in patients with hypercholesterolaemia. Significant positive correlations existed between serum total cholesterol and TSH, FSH or LH, even after adjusting for confounding factors. Taken together, the results of the present study suggest that the high‐cholesterol diet affected the levels of hormones derived from anterior pituitary basophilic cells. This phenomenon might contribute to the pituitary functional disturbances described in hypercholesterolaemia.     

成年男性癫痫患者血清性腺激素水平的变化

目的： 探讨癫痫发作和ＡＥＤｓ 治疗对垂体一性腺激素平衡的影响。方法： 利用ＲＩＡ法测定了诊断明确的７３ 例成年男性癫痫患者血清ＬＨ、ＦＳＨ、Ｐ、Ｅ２、Ｔ水平, 并比较了ＡＥＤｓ 治疗组与未治疗组和健康对照组病人的血清性腺激素水平。同时,观察了其中的３１ 例癫痫患者癫痫发作前后血清性腺激素水平的变化。结果：癫痫发作前后血清性腺激素水平无明显差异。ＡＥＤｓ 明显影响血清性腺激素水平。在所有ＡＥＤｓ 治疗中, 血清Ｅ２ 水平明显升高, ＬＨ水平明显减低, Ｔ／Ｅ２ 的比较明显低于正常对照和病人对照组, 在ＡＥＤｓ 单一和联合治疗组中有３９．７％ 的病例性功能低下。结论： 癫痫发作不影响血清性腺激素水平。ＡＥＤｓ明显影响性激素平衡和性功能     

Changes in anterior pituitary function during ACTH therapy of patients with infantile spasms

Serum cortisol, prolactin (PRL), TSH, GH, LH and FSH levels were measured before and immediately after daily ACTH-Z therapy (0.01 mg/kg/day, 1-2 weeks) for 5 patients with infantile spasms and one patient with myoclonus epilepsy. Total number of ACTH-Z therapy were 8 times, and all patients became seizure free after ACTH-Z therapy. In 6 occasions, TRH, LH-RH and insulin tolerance tests were performed before and after daily ACTH-Z therapy. Serum cortisol levels were significantly increased after daily ACTH-Z therapy but all other hormone levels were significantly decreased. In TRH and LH-RH tolerance tests, peak levels and increments of PRL, LH and FSH were significantly decreased after daily ACTH-Z therapy and those of TSH were mildly decreased. In one case insulin tolerance test revealed an adequate decrease of blood glucose before and after ACTH-Z therapy, and there was a poor GH response after ACTH-Z therapy. Daily ACTH-Z therapy was thought to suppress secretion of anterior pituitary hormones.     

Seasonal Effect of Gonadotrophin Inhibitory Hormone on Gonadotrophin‐Releasing Hormone‐induced Gonadotroph Functions in the Goldfish Pituitary

We have shown that native goldfish gonadotrophin inhibitory hormone (gGnIH) differentially regulates luteinsing hormone (LH)‐β and follicle‐stimulating hormone (FSH)‐β expression. To further understand the functions of gGnIH, we examined its interactions with two native goldfish gonadotrophin‐releasing hormones, salmon gonadotrophin‐releasing hormone (sGnRH) and chicken (c)GnRH‐II in vivo and in vitro. Intraperitoneal injections of gGnIH alone reduced serum LH levels in fish in early and mid gonadal recrudescence; this inhibition was also seen in fish co‐injected with either sGnRH or cGnRH‐II during early recrudescence. Injection of gGnIH alone elevated pituitary LH‐β and FSH‐β mRNA levels at early and mid recrudescence, and FSH‐β mRNA at late recrudescence. Co‐injection of gGnIH attenuated the stimulatory influences of sGnRH on LH‐β in early recrudescence, and LH‐β and FSH‐β mRNA levels in mid and late recrudescence, as well as the cGnRH‐II‐elicited increase in LH‐β, but not FSH‐β, mRNA expression at mid and late recrudescence. sGnRH and cGnRH‐II injection increased pituitary gGnIH‐R mRNA expression in mid and late recrudescence but gGnIH reduced gGnIH‐R mRNA levels in late recrudescence. gGnIH did not affect basal LH release from perifused pituitary cells and continual exposure to gGnIH did not alter the LH responses to acute applications of GnRH. However, a short 5‐min GnIH treatment in the middle of a 60‐min GnRH perifusion selectively reduced the cGnRH‐II‐induced release of LH. These novel results indicate that, in goldfish, gGnIH and GnRH modulate pituitary GnIH‐R expression and gGnIH differentially affects sGnRH and cGnRH‐II regulation of LH secretion and gonadotrophin subunit mRNA levels. Furthermore, these actions are manifested in a reproductive stage‐dependent manner.     

Short-Term Regulation of Gonadotropin Subunit mRNA Levels by Estrogen: Studies in the Hypothalamo-Pituitary Intact and Hypothalamo-Pituitary Disconnected Ewe

In this study the levels of mRNA for the pituitary gonadotropin hormone subunits luteinizing hormone β (LHβ), follicle stimulating hormone β (FSHβ) and the common α-subunit were assessed during the acute feedback stages of estradiol benzoate (EB) action in ovariectomized (OVX) ewes with and without hypothalamo-pituitary disconnection (HPD). In OVX/HPD ewes maintained on hourly pulses of 250 μg of gonadotropin-releasing hormone (GnRH) a single i.m. injection of EB in oil caused a biphasic (decrease and then increase) change in plasma LH levels and a monophasic decrease in FSH levels. There was a decrease in pituitary α-subunit and FSHβ mRNA levels during the acute negative (8 h post EB) and through the positive feedback (20 h post EB) stages of the response. No significant change was seen in LHβ mRNA levels following treatment with EB. In hypothalamic-pituitary intact OVX ewes the same EB treatment as above caused a biphasic change in LH secretion with the positive feedback component being much greater than in GnRH-pulsed OVX-HPD ewes. The levels of mRNA for all three gonadotropin subunits were reduced by 8 h after EB injection and remained low throughout the positive feedback period. These data suggest that the LH surge in this experimental model does not require an increase in LHB mRNA levels. Furthermore, the fall in LHβ subunit mRNA seen after estrogen injection to OVX ewes is most likely due to an effect of estrogen to decrease GnRH secretion, since pulsatile GnRH replacement prevents this effect. These data also show that estrogen feedback can effect rapid alterations in pituitary gonadotropin subunit mRNA levels. Short-term changes in FSHβ mRNA are reflected in changes in FSH secretion; the same is not true for LH.     

Altered functional responses with preserved morphology of gonadotrophic cells in congenitally athymic mice

Neonatal thymectomy or congenital absence of the thymus induces severe reproductive deficiencies in female mice, which are associated with reduced levels of circulating and pituitary gonadotropins. In contrast, the reproductive function is well preserved in nude males. It was therefore of interest to assess gonadotrophic cell morphology and function in congenitally athymic male mice. Circulating gonadotropins were measured under basal and stressful conditions, taking as a reference their haired counterparts. Adult normal (+/+), heterozygous nude (nu/+), and homozygous (nu/nu) CD-1 mice were subjected to 1-h immobilization stress. Serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were assessed by RIA at 0, 30, and 60 min poststress. Athymic animals showed significantly lower basal levels of serum LH and FSH than their heterozygous littermates. Immunohistochemical assessment of LH and FSH cell populations revealed a normal morphology and cell number in the athymic animals compared to their normal littermates. Immobilization stress induced a significant reduction in gonadotrophin levels, particularly LH, in normal mice but had only a weak effect in athymic animals. It is concluded that congenital athymia in the adult male mouse is associated with decreased basal levels of serum LH and FSH, in the presence of a normal gonadotroph number and morphology. The anomalous responses of athymic mice to stress do not appear to be due to primary hypopituitarism but, rather, to an altered modulation of pituitary hormone secretion. .     

Acute hemorrhage and ischemic necroses in hypophyseal tumors: hypophyseal apoplexy

Acute enlargement of pituitary adenomas due to haemorrhage or ischaemic necrosis in the tumour was described as "pituitary apoplexy" by Brougham et al. in 1950. Since then, more than 200 cases have been reported, but--especially in the German literature--the syndrome has caught only little attention. Therefore, in a series of 12 own patients, typical findings and clinical characteristics are demonstrated and the literature is discussed. 9 patients had a haemorrhage into the tumour, 3 an acute ischaemic necrosis. The guiding symptom was the acute onset with ophthalmoplegia (11 of 12 patients). Only in one case the adenoma was known before the apoplexy. Other symptoms were headache, blurred vision, drowsiness and, in severe cases, hemiparesis, coma, and hypothalamic disorder. Most important is the acute endocrinological substitution with hydrocortisone; this may be life-saving. Neuroophthalmological recovery depends on early operation: cases of oculomotor palsy require an operation within the first 2 weeks after the acute event. An emergency operation is required only by an acute amaurosis. In general there will be enough time for careful clinical endocrinological and radiological investigations.     

Pituitary apoplexy as a cause of internal carotid artery occlusion.

Occlusion of intracranial arteries by pituitary apoplexy with resulting infarction is a rare occurrence. A 50-year-old man who presented with a history of sudden onset of frontal headache and visual impairment was admitted to another medical centre and MRI revealed a non-enhancing sellar lesion with suprasellar and infrasellar extension. Thereafter, the patient's consciousness deteriorated progressively and he showed signs of herniation; he was then referred to our centre for further evaluation. CT scanning revealed infarction of the left internal carotid artery territory. Transcranial resection of the tumour followed by a large decompressive craniotomy restored the blood flow in the internal carotid artery. Histological examination revealed the tumour to be a pituitary adenoma that contained formed blood elements. The patient's neurological status did not improve and he died on the ninth postoperative day despite vigorous treatment for controlling intracranial pressure. This case study documents a rare presentation of pituitary apoplexy that caused signs of raised intracranial pressure due to mechanical obstruction of an internal carotid artery with resulting infarction.     

Effects of Carbamazepine on the Hypothalamic-Pituitary-Gonadal Axis in Male Patients with Epilepsy: A Prospective Study

The effects of carbamazepine (CBZ) monotherapy on serum sex hormone levels and on pituitary responsiveness to various stimuli were evaluated in a prospective study with 21 male patients with epilepsy. The serum levels of testosterone (T), free testosterone (FT), sex hormone binding globulin (SHBG), estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), and dehydroepiandrosterone sulfate (DHEAS) were assayed, and the free androgen index (FAI) values were calculated for each patient before and after 2-month CBZ treatment. The pituitary PRL, LH, and FSH responses to luteinizing hormone-releasing hormone (LH-RH), thyrotropin-releasing hormone (TRH), and metoclopramide (MC) were also measured before and after CBZ treatment. The baseline serum hormone and SHBG levels were measured and the FAI values calculated in 16 healthy male control subjects of similar age. The mean E2 level was higher in patients before CBZ treatment than in control subjects, and untreated patients had greater variances for FAI values, PRL levels, and LH levels than control subjects. No other significant differences were found between untreated patients and control subjects. The FAI values and DHEAS levels of patients decreased during 2-month treatment with CBZ. The PRL response to MC was higher after CBZ treatment than before. The baseline levels of other hormones and SHBG, as well as the LH and FSH responses to LH-RH, remained unaltered. The results indicate that during the first 2 months of CBZ treatment the androgen balance in male epileptic patients changes: Serum DHEAS levels and FAI values decrease, although FT levels remain unchanged. The clinical relevance of these hormonal changes is obscure.     

Coexistence of aneurysmal subarachnoid haemorrhage and pituitary apoplexy: Case report and review of the literature.

A case of aneurysmal subarachnoid haemorrhage with associated haemorrhagic infarction of a growth hormone secreting pituitary macroadenoma is presented. The subarachnoid haemorrhage was not identifiable on CT, but was apparent on MRI. Angiography revealed a 7mm right posterior communicating aneurysm, a 3mm left A1 segment anterior cerebral aneurysm, and vasospasm. Surgery was performed through a right pterional/subfrontal approach, clipping both aneurysms and debulking the tumour. The left A1 aneurysm was the site of subarachnoid haemorrhage. There was evidence of haemorrhagic infarction of the pituitary tumour. Although rupture of an aneurysm into a pituitary tumour has been previously reported, this is the first case reported of aneurysmal subarachnoid haemorrhage with coexisting pituitary apoplexy where the aneurysm had not bled directly into the pituitary tumour. The literature regarding the association between pituitary tumours and aneurysm is reviewed.     

Secretion of neuron-specific enolase, prolactin, growth hormone, luteinising hormone and follicle stimulating hormone by "functionless" and endocrine-active pituitary tumours in vitro.

Secretion of the neuroendocrine marker neuron-specific enolase by 24 pituitary tumours was measured in maintenance tissue culture. Eleven endocrine-active and 13 "functionless" tumours were defined by measurement of prolactin, growth hormone, luteinising hormone (LH) and follicle stimulating hormone (FSH) secretion rates in vitro and the corresponding plasma hormone levels. Measurement of prolactin secretion provided a clear distinction between true prolactinomas and "functionless" tumours causing hyperprolactinaemia by stalk compression (pseudoprolactinomas). A previous report of LH and/or FSH secretion by the majority of "functionless" tumours was confirmed, but plasma levels of LH and FSH were usually normal. It is argued that LH and FSH are not the major hormones secreted by "functionless" tumours. A high production rate of neuron-specific enolase appears to be characteristic of the cell type from which most "functionless" tumours derive.     

Ischemic pituitary apoplexy associated with the lupus anticoagulant

PURPOSE: To report a case of ischemic pituitary apoplexy secondary to a hypercoagulable state following elective orthopedic surgery. DESIGN: Observational case report. METHODS: A 48-year-old Caucasian man underwent an uneventful, left-sided total hip replacement and corrective osteotomy of the proximal femur. Two days post-operative, he developed a frontal headache and blurred vision in both eyes. RESULTS: Ophthalmic examination revealed right VIth cranial nerve palsy. Imaging studies indicated pituitary apoplexy with a large hypodense pituitary lesion with widening of the sella turcica. Laboratory findings included positive lupus anticoagulant, a normal prothrombin time (PT), and an elevated activated partial thromboplastin time (aPTT). Five days after the initial symptoms, a transsphenoidal pituitary resection was performed. At a 6 months follow-up, the VIth nerve paresis was completely resolved. CONCLUSIONS: This case describes ischemic pituitary apoplexy associated with a pre-operatively elevated aPTT and positive lupus anticoagulant. This is the first report, to our knowledge, of atypical apoplexy concurrent with antiphospholipid (aPL) antibodies following an uneventful surgery. The results we obtained on this patient suggest that an associated hypercoaguable state may increase the risk of thrombosis following elective orthopedic surgery.     

Gonadotropin response to synthetic gonadotropin hormone-releasing hormone (GnRH) in heroin addicts.

To determine whether the pituitary-gonadal deficiency in heroin addicts is related to heroin's effect on the hypothalamus, the authors administered gonadotropin hormone-releasing hormone (GnRH) to 10 male heroin addicts and 5 controls and measured follicle-stimulating hormone (FSH) and luteinizing hormone (LH) response. Basal FSH and LH levels were significantly lower in addicts; after GnRH stimulation the addicts' FSH and LH values increased but not significantly compared to controls. The difference between the two groups' response was highly significant. The authors suggest that heroin causes an incomplete blocking of gonadotropin secretion at the pituitary level, inducing a hypophyseal-gonadal deficiency and a long-lasting depletion of the endogenous releasing factor, which accounts for the reduced response to GnRH.     

Sexual maturation modifies the GABAergic control of gonadotrophin secretion in female rats

Administration of aminooxyacetic acid, (an inhibitor of γ-aminobutyric acid (GABA)-transaminase which enhances the hypothalamic GABA content) increased luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in prepubertal rats (16 days of age), and decreased the levels of these pituitary hormones in peripubertal rats (30 days of age). Prepubertal and peripubertal female rats were administered with muscimol, a GABA_A-antagonist, with baclofen, a GABA_B agonist, and with bicuculline, a GABA-antagonist, and the serum concentrations of LH and FSH were determined. In prepubertal rats, muscimol increased both LH and FSH levels, while in peripubertals the GABA_A agonist showed the opposite effect, i.e. both gonadotrophins were decreased after its administration. Baclofen lowered serum concentrations of LH and FSH at the different ages studied. Administration of bicuculline produced a decrease in LH and FSH concentrations in prepubertal rats, and an increase of these values in peripubertal rats. These results indicate that GABA exerts a stimulatory tone on gonadotrophin secretion in prepubertal rats and an inhibitory one in peripubertal animals. This effect is most probably mediated by GABA_A receptors. It is suggested that the change in the effect on gonadotrophin secretion of the activation of GABA_A receptors which takes place during sexual maturation in the female rats is related to the central mechanisms involved in the onset of puberty.     

Pituitary Gonadotrophic Hormone Synthesis,Secretion, Subunit Gene Expression and Cell Structure in Normal and Follicle‐Stimulating Hormone β Knockout,Follicle‐Stimulating Hormone Receptor Knockout,Luteinising Hormone Receptor Knockout,Hypogonadal and Ovariectomised Female Mice

To investigate the relationship between gonadotroph function and ultrastructure, we have compared, in parallel in female mice, the effects of several different mutations that perturb the hypothalamic‐pituitary‐gonadal axis. Specifically, serum and pituitary gonadotrophin concentrations, gonadotrophin gene expression, gonadotroph structure and number were measured. Follicle‐stimulating hormone β knockout (FSHβKO), follicle‐stimulating hormone receptor knockout (FSHRKO), luteinising hormone receptor knockout (LuRKO), hypogonadal (hpg) and ovariectomised mice were compared with control wild‐type or heterozygote female mice. Serum levels of LH were elevated in FSHβKO and FSHRKO compared to heterozygote females, reflecting the likely decreased oestrogen production in KO females, as demonstrated by the threadlike uteri and acyclicity. As expected, there was no detectable FSH in the serum or pituitary and an absence of expression of the FSHβ subunit gene in FSHβKO mice. However, there was a significant increase in expression of the FSHβ and LHβ subunit genes in FSHRKO female mice. The morphology of FSHβKO and FSHRKO gonadotrophs was not significantly different from the control, except that secretory granules in FSHRKO gonadotrophs were larger in diameter. In LuRKO and ovariectomised mice, stimulation of LHβ and FSHβ mRNA, as well as serum protein concentrations, were reflected in subcellular changes in gonadotroph morphology, including more dilated rough endoplasmic reticula and fewer, larger secretory granules. In the gonadotophin‐releasing hormone deficient hpg mouse, gonadotrophin mRNA and protein levels were significantly lower than in control mice and gonadotrophs were correspondingly smaller with less abundant endoplasmic reticula and reduced numbers of secretory granules. In summary, major differences in pituitary content and serum concentrations of the gonadotrophins LH and FSH were found between control and mutant female mice. These changes were associated with changes in expression of the gonadotrophin subunit genes and were reflected in the cellular structure and secretory granule appearance within the gonadotroph cells.