Multiple Pituitary Hormone Gradients from Cavernous Sinus Sampling in Patients with Cushing's Disease

Summary  Objective. Cavernous sinus sampling in patients with adrenocorticotropic-hormone (ACTH) secreting pituitary adenomas has been used to identify directly ACTH hypersecretion from the pituitary and to predict the lateralization of a microadenoma. In our previous series, cavernous sinus sampling provided a sufficient central/peripheral (c/p) ratio of ACTH and the correct laterality of the pituitary lesion in all microadenomas situated in the lateral wing. To clarify the diagnostic value of other anterior pituitary hormones in relation to ACTH gradients, we evaluated multiple pituitary hormone gradients between a cavernous sinus and a peripheral vein and between both cavernous sinuses in patients with Cushing's disease.  Methods. Cavernous sinus sampling was done in 11 patients with clinical and biochemical features of ACTH-dependent Cushing's syndrome. In 9, pituitary adenoma was detected during transsphenoidal surgery and histologically confirmed, while 2 others were suspected of having ectopic lesions. Serum ACTH, prolactin (PRL), thyroid stimulating hormone (TSH), growth hormone (GH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) from catheters in both cavernous sinuses and from a peripheral vein were measured. The c/p ratios of each hormone and the intercavernous gradients were evaluated.  Results. The c/p ratio of ACTH indicated the presense of pituitary lesions in all 9 patients with ACTH-secreting microadenomas. In addition, the intercavernous gradients of ACTH indicated the correct localization of microadenomas in all 6 patients with lateralized lesions. As for other hormones, the c/p ratios of GH, PRL, TSH and LH were significantly high in number 7, 6, 6 and 3 patients, respectively. In contrast, the significant step up of FSH was observed only in one patient. The intercavernous gradients of GH and PRL were significantly high in number 5 and 4 patients, respectively.  Conclusions. The intercavernous gradients of GH and PRL tend to indicate the lateralization of a microadenoma. The measurement of GH and PRL during cavernous sinus sampling may provide additional information, in the lateralization of ACTH-secreting microadenomas.     

Physiology of the pituitary, thyroid and adrenal glands

The pituitary gland is made of clusters of cells producing specific hormones that control growth (growth hormones, GH), thyroid function (TH), adrenal function (ACTH), gonadal function (FSH and LH). In addition, the neurons that join the posterior pituitary (neurohypophysis) secrete vasopressin - the antidiuretic hormone involved in maintaining water balance.The negative feedback loop is the basic mechanism to control the regulation of all endocrine glands. Hypothalamic peptides - releasing hormones (e.g. TRH, CRH) reach the hypophysis via the portal venous system and induce the secretion of specific stimulating hormones (e.g. TSH, ACTH) that drive the end-target endocrine cells to secrete hormones (e.g. thyroid hormones - T3 and T4 or adrenal hormones - cortisol, DHEAS). The plasma levels of these circulating hormones inhibit the pituitary (short feedback) or the hypothalamus (long feedback) and limit the further release of releasing- and stimulating- hormones.The effects of circulating hormones on different tissues are mediated via specific receptors on the cell membrane (e.g. vasopressin receptors), in the cytoplasm (steroid receptor for cortisol) or in the nucleus (e.g. thyroid hormone receptors). Understanding the physiological effects of peripheral hormones helps understanding the mechanisms by which clinical signs and symptoms developed in diseases characterised by excessive hormone secretion (e.g. thyrotoxicosis, Cushing syndrome, phaeochromocytomas) or lack of hormone secretion (e.g. diabetes insipidus).     

A case of pleomorphic TSH-producing pituitary adenoma with calcification

We reported a rare case of pleomorphic TSH-producing pituitary adenoma with calcification and reviewed the literature. A 25-year-old female was admitted to our hospital with a complaint of anterior neck swelling. An endocrinological examination demonstrated elevated serum levels of free triiodothyronine (FT3: 5.6 pg/ml), free thyroxin (FT4: 2.2 ng/dl), TSH (5.85 microIU/ml), and TSH a-subunit (5.9 ng/ml), whereas a physical examination revealed no goiter. CT scan showed a suprasellar isodensity mass with dense calcification. Contrast-enhanced T1-weighted images revealed a less enhancing tumor extending from the left upper portion of pituitary fossa into suprasellar cistern. The patient underwent gross total removal of the tumor via the right pterional approach. Microscopically, medium-sized to enlarged tumor cells with marked pleomorphism and prominent calcification were observed.The tumor cells displayed positive reaction for TSH (beta-subunit). The MIB-1 index averaged 2.9%. The histological diagnosis was a pleomorphic TSH-producing pituitary adenoma. Postoperatively, the serum levels of FT3, FT4, TSH, and TSH alpha-subunit decreased to normal range. Follow-up MR images showed no evidence of recurrent tumor 3 years after the resection. All of six patients with densely calcified TSH-producing pituitary adenoma, previously reported in the literature, remained well without tumor recurrence. We suggest that this type of TSH-producing pituitary adenoma may be associated with favorable prognosis despite histologically pleomorphic appearance.     

Anterior pituitary hormone in severe head injury--with special reference to the GH, TSH, LH and FSH response to TRH and LH-RH

Measurement of the serum level of anterior pituitary hormones (GH, TSH, LH and FSH) and the response of these hormones to their releasing hormones were made in 45 uncomplicated head injury patients within 24 hours after injury. We classified these 45 patients into three groups according to the Glasgow Outcome Scale of six months after head injury, such as good outcome group (GR or MD), poor outcome group (SD or PVS) and dead group. The serum level of the anterior pituitary hormones in dead group were higher than those in the good or poor outcome group, especially the level of GH. The serum level of GH was 14.7 +/- 3.0 ng/ml in the dead group, whereas 5.8 +/- 0.9 ng/ml in the good outcome group and 4.0 +/- 2.1 ng/ml in the poor outcome group. The response of TSH, LH or FSH to the administration of TRH or LH-RH were depressed in the dead group. On the other hand, there were normal response of TSH, LH or FSH following administration of TRH or LH-RH in the other two survival groups. These findings suggested that the measurement of the anterior pituitary hormones and the response of these hormones to their releasing hormones were useful to evaluate the severity of head injury.     

Influence of obesity and surgical weight loss on thyroid hormone levels

BACKGROUND: The pathophysiologic relationship between morbid obesity and thyroid hormones is not well understood. The goal of this study was to evaluate the influence of obesity and weight reduction after bariatric surgery on thyroid hormone levels. METHODS: Patients who underwent gastric bypass or adjustable gastric banding at our institution, had no previous diagnosis of thyroid disorder, were not taking medication that could affect the thyroid function evaluation, and who were nonsmokers were included in this retrospective evaluation. The association between the thyroid-stimulating hormone (TSH) and free thyroxine (T(4)) levels and body mass index (BMI), and the influence of weight loss after bariatric surgery on these hormones were investigated at different points (preoperatively and 6 and 12 months after bariatric surgery). RESULTS: A total of 86 patients met the study criteria. The TSH levels correlated positively with BMI (P <.001, r = .91) within the BMI range of 30-67 kg/m(2). The mean BMI change from 49 to 32 kg/m(2) after bariatric surgery was associated with a mean reduction in the TSH level from 4.5 to 1.9 microU/mL. Free T(4) showed no association with BMI and was not significantly influenced by weight loss. Before bariatric surgery, 10.5% of the subjects had laboratory values consistent with subclinical hypothyroidism. After bariatric surgery, 100% of these patients experienced significant weight reduction with simultaneous resolution of their subclinical hypothyroidism. CONCLUSION: The results of our study have demonstrated a statistically significant positive association between serum TSH within the normal range and BMI. No association was found between BMI and free T(4) serum levels. The prevalence of subclinical hypothyroidism in study group was 10.5%. Weight loss after bariatric surgery improved or normalized thyroid hormone levels.     

Two cases of TSH-secreting pituitary adenoma; endocrinological, diagnostic and therapeutic approach to the disease

Two cases of TSH-secreting pituitary adenoma were reported. Endocrinological and immunohistochemical features of these cases were described and problems in diagnosis and treatment of the rare disease are discussed. [case 1] A 28 year-old woman suffered from hyperthyroidism with a relatively high value of serum TSH (T3; 350 ng/dl, T4; 10.0 micrograms/dl, TSH; 24.5 microU/ml). She was treated with antithyroid drug and then underwent subtotal thyroidectomy. Although the levels of serum T3 and T4 were lowered to within normal range, the level of serum TSH still remained high. One month later, she developed frontal headache, amenorrhea and bitemporal hemianopsia. A CT scan showed an enhanced mass in the sellar and suprasellar region. Preoperative endocrinological studies showed elevated values of TSH (47 microU/ml) and its alpha-subunit (9.0 ng/ml). The levels of both T3 (190 ng/dl) and T4 (10.0 micrograms/dl) were near the upper normal limit. Serum TSH was suppressed by administration of exogenous T3, but did not respond to exogenous TRH, l-Dopa nor bromocriptine. Under the diagnosis of TSH-secreting pituitary adenoma, the patient was operated on by craniotomy and received local radiation therapy (50 Gy). In 1990, 12 years after the treatment, she is well and endocrinologically normal. Immunohistochemical study revealed that most tumor cells were positive for TSH. [case 2] A 28 year-old woman visited our hospital for examination of hyperthyroidism. Serum level of TSH was detectable (4.5 microU/ml). A CT scan performed at that time disclosed no pituitary tumor. Thyroid function was normalized by antithyroid drug, but the level of TSH was still high and progressively increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Usefulness of inferior petrosal sinus venous endocrine markers in Cushing's disease

Bilateral and simultaneous sampling of the inferior petrosal sinuses in patients with Cushing's disease has been used to establish the presence and laterality of adrenocorticotropic hormone (ACTH)-producing microadenomas prior to transsphenoidal surgery. Successful preoperative lateralization depends upon equivalent dilution of pituitary venous blood on the two sides since samples which are diluted by unequal amounts of non-pituitary blood may lead to erroneous results. To assure valid sampling results, the use of other pituitary hormones, measured simultaneously, has been proposed to correct the ACTH concentrations from the inferior petrosal sinuses against unequal dilution by non-pituitary venous blood. This proposal presumes that ACTH-secreting microadenomas will not cause unequal delivery of the other pituitary hormones into the two inferior petrosal sinuses. The inferior petrosal sinus concentrations of prolactin (PRL), thyrotropin (TSH), and the alpha subunit of human chorionic gonadotropin (alpha-HCG) were evaluated as indicators of pituitary venous blood dilution in 11 patients with Cushing's disease. Four patients with ectopic ACTH syndrome served as controls. Blood was withdrawn simultaneously from catheters in both inferior petrosal sinuses and from a peripheral vein for measurement of ACTH, PRL, TSH, and alpha-HCG. The ACTH concentrations were then corrected for dilution by non-pituitary blood by dividing the ACTH concentration from each side by the ratio of the inferior petrosal sinus to peripheral blood concentrations of PRL, TSH, and alpha-HCG for that side. At surgery, all 11 patients had ACTH-secreting microadenomas on the side predicted by the uncorrected ACTH concentrations. However, in three patients the corrected ACTH values would have led to erroneous results. Among the 18 sets of corrected inferior petrosal sinus measurements in these three patients, the corrected ACTH values failed to show an inferior petrosal sinus gradient in six and localized the tumor to the side opposite the adenoma in four. Incorrect lateralization was obtained with each of the hormones (PRL, TSH, and alpha-HCG) used for correction. Furthermore, the ipsilateral (side of tumor)-to-contralateral inferior petrosal sinus gradient of ACTH in patients with Cushing's disease was generally paralleled by a significant inferior petrosal sinus gradient of PRL, TSH, and alpha-HCG to the side of the tumor, whereas patients with the ectopic ACTH syndrome tended not to exhibit lateralizing (side-to-side) gradients.(ABSTRACT TRUNCATED AT 400 WORDS)     

甲状腺腺瘤术后内分泌治疗的研究

目的 探讨甲状腺腺瘤术后内分泌治疗的必要性。方法 对１００例次手术后甲状腺腺瘤标本用ＳＰ法测定ＴＳＨ受体,瘤体周围的甲状腺组织连续病理切片检查有无存在微小瘤灶,并按随机抽签法将病人分成Ａ、Ｂ两组,Ａ组口服甲状腺片治疗,Ｂ组不用任何治疗。术后定期测定血Ｔ３,Ｔ４,ＴＳＨ浓度,＾１３１Ｉ扫描及Ｂ超检查残存甲状腺。结果 甲状腺瘤１００％存在ＴＳＨ受体,８％有微小瘤灶。Ａ组病人血Ｔ３,Ｔ４,ＴＳＨ及残存甲     

Relationships between serum hormone levels and semen quality among men from an infertility clinic

Participation rates in epidemiologic studies on semen quality are generally very low, raising concerns as to the potential for selection bias. Since hormones both initiate and maintain spermatogenesis, they may serve as surrogates of semen quality in epidemiologic studies. For this reason, in the present study, we explored the influence and predictive ability of reproductive and thyroid hormones on semen quality among men who were partners in an infertile couple. Between 1999 and 2003, 388 men were recruited from Massachusetts General Hospital Andrology Laboratory for clinical evaluation of fertility status. Fresh semen samples were assessed for quality (concentration, motility and morphology) and the serum levels of hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, sex hormone-binding globulin (SHBG), testosterone, free androgen index, free T4, total T3, and thyroid-stimulating hormone (TSH), were measured. Multiple logistic regression revealed increased odds for below-reference sperm concentration and morphology in men with increased FSH, and decreased odds for below-reference sperm concentration and motility in men with increased inhibin B. When FSH and inhibin B were divided into quintiles, the relationships with sperm concentration showed evidence of a threshold value. However, the ability of specific FSH (10 IU/L) and/or inhibin B (80 pg/mL) cutoff values to predict semen quality was lower than in previous reports. In multiple linear regression analysis, FSH and LH were inversely associated with sperm concentration, motility, and morphology. Inhibin B and free T4 were positively associated with sperm concentration, while there was a suggestive positive association between testosterone and sperm motility. In conclusion, we have found that FSH, LH, inhibin B, testosterone and free T4 levels are associated with human semen parameters. Additional consideration should be given to the utility of serum hormone levels as a surrogate for semen quality in epidemiologic studies in which the collection of semen is difficult due to logistical and/or volunteer rate constraints.     

促甲状腺激素型垂体腺瘤的临床诊疗特点

目的 研究促甲状腺激素(TSH)型垂体腺瘤的临床诊断和治疗特点.方法 回顾性分析2001年1月至2008年12月收治的19例TSH型垂体腺瘤患者的临床资料.男性14例,女性5例;年龄20～70岁,平均40.5岁;病程1～228个月,平均55个月.15例患者因甲状腺功能亢进(甲亢)症状就诊,其中12例被误诊为原发性甲亢并口服抗甲亢药物治疗,另3例入院后很快确诊.4例患者因头痛和视力视野障碍等肿瘤占位效应就诊.在12例误诊患者中,2例行131I放射性核素治疗,1例行甲状腺大部分切除.所有患者均行经蝶垂体腺瘤切除术.结果 病理均为垂体腺瘤,免疫组化TSH阳性17例,阴性2例,生长激素阳性2例,泌乳素阳性1例,促肾上腺皮质激素阳性1例.术后MRI显示肿瘤全切除15例,肿瘤残留4例.随访时间6个月～7年,平均3.6年.术后3个月内甲状腺激素水平各项均正常13例,其中2例3个月后复查TSH再次升高,但MRI未见肿瘤复发,行垂体放疗后甲状腺各项激素均正常.手术治愈率11/19,手术加放疗治愈率13/19.结论 对合并TSH升高的甲亢患者的筛查是提高TSH型垂体腺瘤的早期诊断的关键.治疗采用以手术治疗为主,垂体放疗和生长抑素为辅的治疗方法.     

促甲状腺激素型垂体腺瘤的临床诊疗特点

目的 研究促甲状腺激素(TSH)型垂体腺瘤的临床诊断和治疗特点.方法 回顾性分析2001年1月至2008年12月收治的19例TSH型垂体腺瘤患者的临床资料.男性14例,女性5例;年龄20～70岁,平均40.5岁;病程1～228个月,平均55个月.15例患者因甲状腺功能亢进(甲亢)症状就诊,其中12例被误诊为原发性甲亢并口服抗甲亢药物治疗,另3例入院后很快确诊.4例患者因头痛和视力视野障碍等肿瘤占位效应就诊.在12例误诊患者中,2例行131I放射性核素治疗,1例行甲状腺大部分切除.所有患者均行经蝶垂体腺瘤切除术.结果 病理均为垂体腺瘤,免疫组化TSH阳性17例,阴性2例,生长激素阳性2例,泌乳素阳性1例,促肾上腺皮质激素阳性1例.术后MRI显示肿瘤全切除15例,肿瘤残留4例.随访时间6个月～7年,平均3.6年.术后3个月内甲状腺激素水平各项均正常13例,其中2例3个月后复查TSH再次升高,但MRI未见肿瘤复发,行垂体放疗后甲状腺各项激素均正常.手术治愈率11/19,手术加放疗治愈率13/19.结论 对合并TSH升高的甲亢患者的筛查是提高TSH型垂体腺瘤的早期诊断的关键.治疗采用以手术治疗为主,垂体放疗和生长抑素为辅的治疗方法.

Abstract：

Objective To study the clinical characteristics, diagnosis and surgical effects of thyroid-stimulating hormone pituitary adenomas (TSH-omas). Methods The clinical data of 19 patients (14 female and 5 male) with TSH-omas were analyzed retrospectively in this study from January 2001 to December 2008. The patients ranged from 20 to 70 years old ( average 40. 5 years old) and had disease histories from 1 to 228 months (average 55 months). Among these patients, 15 of them complained of thyrotoxicosis symptoms, while the other 4 patients' symptoms were associated with headache and/or visual disturbance caused by the tumor mass effect. Initially, 12 of the 15 patients with thyrotoxicosis symptoms were misdiagnosed with Grave's disease. As a result 2 of them received 131Iodine, and one received subtotal thyroidectomy. All of these patients underwent transsphenoidal microsurgery. Results Average follow-up period was 3. 6 years (6 months-7 years). Pathological analysis of the surgical specimen showed pituitary adenoma in all patients, immunohistostains were positive for TSH in 17 cases, negative for TSH in 2,positive for growth hormone in 2, positive for prolactin in 1, and positive for adrenocorticotrophic hormone in 1. Postoperative MRI revealed that the tumors in 15 patients were removed totally, though 4 patients still had residual tumors. The thyroid hormone level tests suggested that 13 patients could be considered normal 3 months after their tumors were removed, though 2 of patients with normal postoperative MRI and thyroid hormones showed increased levels of TSH. For these 2 patients, tumors did not recur and their thyroid hormone levels returned to normal after pituitary radiotherapy. The cure rate was 11/19 after surgery and 13/19 after surgery plus pituitary radiotherapy. Conclusions The screening test for hyperthyroidism patients with high TSH levels is a key point to improve the accuracy rate in early diagnoses of TSH-omas. The transsphenoidal microsurgery is first choice to treat TSH-omas, while pituitary radiotherapy and somatostatin analogs are beneficially adjunctive therapies.     

促甲状腺激素型垂体腺瘤的临床诊疗特点

目的 研究促甲状腺激素(TSH)型垂体腺瘤的临床诊断和治疗特点.方法 回顾性分析2001年1月至2008年12月收治的19例TSH型垂体腺瘤患者的临床资料.男性14例,女性5例;年龄20～70岁,平均40.5岁;病程1～228个月,平均55个月.15例患者因甲状腺功能亢进(甲亢)症状就诊,其中12例被误诊为原发性甲亢并口服抗甲亢药物治疗,另3例入院后很快确诊.4例患者因头痛和视力视野障碍等肿瘤占位效应就诊.在12例误诊患者中,2例行131I放射性核素治疗,1例行甲状腺大部分切除.所有患者均行经蝶垂体腺瘤切除术.结果 病理均为垂体腺瘤,免疫组化TSH阳性17例,阴性2例,生长激素阳性2例,泌乳素阳性1例,促肾上腺皮质激素阳性1例.术后MRI显示肿瘤全切除15例,肿瘤残留4例.随访时间6个月～7年,平均3.6年.术后3个月内甲状腺激素水平各项均正常13例,其中2例3个月后复查TSH再次升高,但MRI未见肿瘤复发,行垂体放疗后甲状腺各项激素均正常.手术治愈率11/19,手术加放疗治愈率13/19.结论 对合并TSH升高的甲亢患者的筛查是提高TSH型垂体腺瘤的早期诊断的关键.治疗采用以手术治疗为主,垂体放疗和生长抑素为辅的治疗方法.     

促甲状腺激素型垂体腺瘤的临床诊疗特点

目的 研究促甲状腺激素(TSH)型垂体腺瘤的临床诊断和治疗特点.方法 回顾性分析2001年1月至2008年12月收治的19例TSH型垂体腺瘤患者的临床资料.男性14例,女性5例;年龄20～70岁,平均40.5岁;病程1～228个月,平均55个月.15例患者因甲状腺功能亢进(甲亢)症状就诊,其中12例被误诊为原发性甲亢并口服抗甲亢药物治疗,另3例入院后很快确诊.4例患者因头痛和视力视野障碍等肿瘤占位效应就诊.在12例误诊患者中,2例行131I放射性核素治疗,1例行甲状腺大部分切除.所有患者均行经蝶垂体腺瘤切除术.结果 病理均为垂体腺瘤,免疫组化TSH阳性17例,阴性2例,生长激素阳性2例,泌乳素阳性1例,促肾上腺皮质激素阳性1例.术后MRI显示肿瘤全切除15例,肿瘤残留4例.随访时间6个月～7年,平均3.6年.术后3个月内甲状腺激素水平各项均正常13例,其中2例3个月后复查TSH再次升高,但MRI未见肿瘤复发,行垂体放疗后甲状腺各项激素均正常.手术治愈率11/19,手术加放疗治愈率13/19.结论 对合并TSH升高的甲亢患者的筛查是提高TSH型垂体腺瘤的早期诊断的关键.治疗采用以手术治疗为主,垂体放疗和生长抑素为辅的治疗方法.     

A case report of adjacent tumor of sphenoid ridge meningioma and GH producing pituitary adenoma

A case of sphenoid ridge meningioma and pituitary adenoma adjacent in the brain is reported. A 70-year-old female was admitted to our hospital with headache. She had no neurological deficit but did have acromegalic change. Hormonal examination showed elevation of plasma levels of HGH (19.0 ng/ml), with normal levels of the other hormones. CT examination revealed a tumor with calcification in the inner third of the sphenoid ridge and another in the pituitary fossa with suprasellar expansion. MRI showed flow void of ICA between these tumors. Intensity of the T1-weighted image of the tumor in the sphenoid ridge was homogeneously iso intensity, and low intensity in the pituitary fossa. The diagnosis of adjacent tumors in the sphenoid ridge meningioma and pituitary adenoma had been made preoperatively. Left front-temporal craniotomy and removal of these tumors were performed. These tumors were close to each other, but were separated by the internal carotid artery and anterior cerebral artery. Pathological examination demonstrated meningotheliomatous meningioma in the sphenoid ridge and sparsely granulated somatotroph adenoma in the pituitary fossa. Fourteen cases showing association of meningioma and pituitary adenoma, which had no history of radiation and trauma, have been reported previously. Although GH producing pituitary adenoma may stimulate adjacent dura and arachnoid cells resulting in the formation of meningioma, the possibility of coincidental occurrence of the two tumors cannot be ignored.     

Spinal bone mass after long-term treatment with L-Thyroxine in postmenopausal women with thyroid cancer and chronic lymphocytic thyroiditis

This study investigated the effect of long-term treatment upon bone density with L-Thyroxine in postmenopausal women compared with untreated postmenopausal women with climacteric symptoms. We measured spinal bone density in three groups (n=84) of postmenopausal women: (A) those treated with TSH-suppressive dosis of L-Thyroxine for a medium of 5 years after removal of thyroid cancer; (B) those on L-Thyroxine treatment for a median of 9 years after being diagnosed with chronic lynfocitic thyroiditis (CLT); and (C) those with no thyroid disease or other known pathology and without any treatment. There were no differences in dietary calcium intake and daily activity between untreated and L-Thyroxine-treated women. Measurements of bone mineral density were performed at spine level L1–L4 using a dual X-ray densitometer and serum thyroid-stimulating hormone (TSH), thyroid hormones, and bone markers (serum osteocalcin, procollagen I, urinary calcium), and PTH levels were assayed and found to be within normal ranges. Women receiving L-Thyroxine after thyroid cancer had slightly higher FT4 levels compared with women who had CLT and lower TSH levels, with serum T4 and T3 levels normal and similar in both groups. No significant differences were found in spinal bone density after L-Thyroxine treatment between Groups A and B and compared with Group C. Bone loss according to 2 SD below reference standards (age and sex matched) was found in the 12.9% of L-Thyroxine-treated patients versus 22.6% of untreated women. No correlation was found between bone loss and thyroid hormone levels and duration of treatment. Our data suggest that long-term L-Thyroxine therapy in postmenopausal women maintaining near physiological levels of thyroid hormones is not associated with significant axial bone loss, therefore other factors should be considered when this occurs.     

Differences in glycoconjugates of adrenocorticotropic hormone-secretory granules between nonadenomatous pituitary cells and adenoma cells as detected by double labeling

Lectin binding sites of adrenocorticotropic hormone (ACTH) secretory granules of human pituitary adenomas and of nonadenomatous pituitary tissue adjacent to adenomas were studied by postembedding immunocytochemical doublestaining on ultrathin sections followed by electron microscopy. The specific hormones produced by the secretory granules were identified by labeling one side of the section with anti-human pituitary hormone antibodies conjugated to gold particles. Simultaneously, the other side was labeled with horseradish peroxidase-lectin to reveal lectin binding sites. Specimens were obtained from four human ACTH-producing pituitary adenomas and from nonadenomatous pituitary tissue surrounding three other adenomas. The four ACTH-producing adenomas showed either weak or negative reactions with concanavalin A, whereas the nonadenomatous ACTH-producing pituitary cells reacted strongly with concanavalin A. Moreover, ACTH secretory granules were significantly larger in the nonadenomatous cells than in adenoma cells. Differences in biochemical structure and ultrastructure between nonadenomatous (normal) pituitary cells and adenoma cells secreting the same specific hormones were demonstrated, and the clinical implications of the results were discussed.     

Endocrinological evaluation of sellar and suprasellar tumor cases (the 2nd report);--on postoperative pituitary function (author's transl)]

Fifty-six cases of sellar and suprasellar tumors were examined endocrinologically before and 3 weeks after surgery. 1) Hyporeactive cases of GH & ACTH were more frequently found in pituitary adenoma (100% and 23% respectively than in craniopharyngioma (86% and 14% respectively) before surgery. 2) GH secretion was impaired 3 weeks after surgery in all the cases. 3) ACTH secretion impaired preoperatively in 5 cases of pituitary adenoma improved in 3 cases 3 weeks after surgery. 4) Hyporeactivity of LH, FSH and TSH was found more frequently after surgery than before. 5) Almost all the cases of tuberculum sellae meningioma were endocrinologically normal before surgery. 6) ACTH, LH, FSH and prolactin secretion in cases of tuberculum sellae meningioma was not impaired after surgery, but TSH secretion in these cases became hyporeative in 4 of 5 cases after surgery.     

Study on testicular tissue in animals with congenital hormone deficiency

Of 3 kinds of animals with congenital hormone deficiency, i.e., mouse with Snell pituitary dwarfism (dw) in which hypoplasia of the pituitary anterior lobe is seen from embryonal stage and which almost lacks in growth hormone (GH), prolactin (PRL), thyroid stimulating hormone (TSH) and adrenocorticotrophic hormone (ACTH); mouse with little dwarfism lacking only in GH (lit); and mouse with congenital primary hypothyroidism in which the thyroidal gland shows hypoplasia, thyroxine (T4) in blood is not measurable and, conversely, TSH level is abnormally high (hyt), the males of dw/dw and hyt/hyt have been proved to be infertile, but it is little known about lit/lit. After performing early recovery experiment by administering GH + T4 to dw/dw, GH to lit/lit and T4 to hyt/hyt from birth, the testicles of 40-day-old mice were investigated morphologically in the normal control group, non-treated group and treated group in order to clarify the relation between hormones and the sperm-generating potency. The total number of sperm-generating cells, which consist of spermatogonia, spermatocytes, spermatids and sperms, showed remarkable decreases, compared with each control group, and the decrease in total cell number was improved favorably by treatment with hormone. In comparison with the control groups, significant decreases were showed in the spermatid number for the dw/dw group, sperm number for the lit/lit group, and spermatid and sperm numbers for the hyt/hyt group. These results indicate that GH and T4 have a potential effect on sperm-generating function.     

A case of pituitary hyperplasia associated with primary hypothyroidism

A thirteen-year-old girl was admitted complaining of short stature and anemia. The low titers of her serum T3 and T4 and the abnormally high TSH level represented primary hypothyroidism. Although she had normal sellar size, CT demonstrated an intra- and suprasellar round mass with homogeneous enhancement. With thyroid replacement therapy the enhanced mass diminished on CT within 5 months, and her symptoms regressed. Twelve cases with radiological diminution of pituitary mass or visual field improvement after thyroid replacement therapy are reviewed. They were considered to be pituitary hyperplasia, rather than pituitary adenoma, caused by long-standing untreated hypothyroidism. In four of them, the pituitary mass on CT was diminished after the therapy. Characteristic CT findings of pituitary hyperplasia, including our case, was a round isodensity mass with homogeneous enhancement in the midline of the pituitary region. In the experimental studies, pituitary hyperplasia is based on the feedback mechanism of hypothalamic-pituitary-thyroid axis, and ultimately autonomous pituitary adenoma may occur. Pituitary mass with hypothyroidism, visual field defect, amenorrhea or galactorrhea tend to be mistaken for prolactinoma or non-functioning adenoma with pituitary hypothyroidism. Thorough endocrinological examination must be carried out. The first choice of treatment for this type of pituitary mass should be thyroid replacement therapy. If there is no improvement of visual field, no regression of pituitary mass on CT, or continuing high TSH levels, then pituitary surgery must be considered.     

Hidradenitis suppurativa: evidence for an endocrine abnormality

Women patients with premenstrual exacerbation of hidradenitis suppurativa have been studied to determine if an endocrine abnormality can be detected. A functional disorder of the hypothalamopituitary axis was found in 13 patients with hidradenitis when compared with 9 controls. In response to a combined thyrotrophin releasing hormone and gonadotrophin releasing hormone test, the prolactin and TSH responses were significantly greater in the hidradenitis patients than the controls. No significant differences were found in the mean basal levels of oestrogen, progesterone, testosterone, dehydroepiandrosterone sulphate, T3 and T4. These results may reflect a disturbance of feedback signals from peripheral hormones, rather than a primary dysfunction of the control of specific anterior pituitary cells.