Thyroid hormone replacement and growth of children with subclinical hypothyroidism and diabetes

Growth potential among people with Type 1 diabetes and subclinical hypothyroidism may be significantly reduced. Growth was evaluated in 25 children with diabetes who had thyromegaly and elevated thyrotrophin (TSH) levels. All patients appeared clinically euthyroid except for four with short stature. Basal growth rate was significantly lower (p less than 0.005) in Group 1 (TSH greater than 50 mU l-1) and Group 2 (TSH level 10.1-50 mU l-1) than in patients with TSH levels between 5 and 10 mU l-1 (Group 3) or control diabetic children. Serum thyroxine (T4) levels were significantly lower (p less than 0.05) in Group 1 than in Groups 2 or 3. Significant improvement in growth velocity after thyroxine treatment was observed in Group 1 patients compared with those in Groups 2 or 3 (p less than 0.05). More prepubertal test children demonstrated improved growth after beginning thyroxine compared with matched diabetic controls (p less than 0.02). Postpubertal subjects treated with thyroxine did not show significant differences in growth velocity compared with controls. Z-scores for height were not different (p greater than 0.05; ANOVA) between control and test patients for any of the groups. Early detection of subclinical hypothyroidism by thyromegaly, reduced growth velocity, and elevated TSH levels, with institution of thyroxine treatment, can improve growth in prepubertal diabetic children.     

Combined bromocriptine and growth hormone (GH) treatment in GH-deficient children with macroprolactinoma in situ.

Experience with PRL-secreting macroadenomas in the pediatric and adolescent population is limited. Although use of synthetic GH after treatment of central nervous system tumors in children without active disease is accepted practice, reports of GH use in patients with central nervous system tumors in situ are rare. Furthermore, the effect of GH on tumor growth is not known. We report GH treatment (10 and 11.5 months), concomitant with bromocriptine (BC; dopamine agonist) therapy in two children, a 15.5-yr-old male and a 15.5-yr-old female, with PRL-secreting macroadenomas in situ. Surgical resection was deemed undesirable because of the risk of major morbidity due to the large size of the tumors and the close proximity to major vessels. Both patients were GH deficient and had heights below the fifth percentile coupled with arrested pubertal progress. During BC therapy, a decrease in tumor size and a reduction in serum PRL levels occurred in both patients, which continued after the addition of GH treatment. Neither patient experienced changes in visual acuity during combined treatment, and both experienced marked improvement in growth velocity. We conclude that in children with PRL-secreting tumors and GH deficiency in whom surgery is not advised, combined treatment with BC and GH appears to be safe and efficacious. To our knowledge, these patients represent the first report of the combined therapeutic use of BC and GH as the primary mode of treatment in children with prolactinoma in situ with documented GH deficiency.     

Growth hormone/insulin-like growth factor axis in patients with subclinical thyroid dysfunction

ObjectiveOur aim was to evaluate serum concentrations of GH, IGF-I, and insulin-like growth factor-binding protein-3 (IGFBP-3) in patients with subclinical thyroid dysfunction before and after normalization of thyroid function.Design and methodsThe study included 51 patients (mean age 42.2 ± 1.8 years) with subclinical hypothyroidism and 30 patients (mean age 44.3 ± 2.4 years) with subclinical hyperthyroidism. A group of 37 euthyroid healthy subjects were studied as controls. Serum concentrations of TSH, FT4, FT3, GH, insulin, IGF-I, and IGFBP-3 were measured in all patients before starting therapy and after normalization of thyroid function. The dosage of levothyroxine (LT4) and antithyroid drugs was adjusted in attempt to keep the serum-free thyroxine (FT4) and thyrotropin (TSH) concentrations within the normal range.Main outcomeBaseline growth hormone levels were similar with hypothyroid group and hyperthyroid group in relation to euthyroid control subjects. Fasting serum IGF-I levels were significantly lower in the subclinical hypothyroid group compared with the control group. On the other hand, IGF-I levels of subclinical hyperthyroid patients and control group were similar. After normalization of thyroid function tests, IGF-I concentrations were increased in subclinical hypothyroid subjects, but unchanged in subclinical hyperthyroid subjects. Patients with subclinical hyperthyroidism showed slightly lower mean serum IGFBP-3 concentrations than those found in control group, but the difference was not statistically significant. Serum GH and IGFBP-3 levels were unaltered by treatment.ConclusionsIn this study, it was shown that GH–IGF axis was not affected in patients with subclinical hyperthyroidism, while it was affected in patients with subclinical hypothyroidism. That is, investigation of the axis in subclinical hyperthyroidism would not bring any extra advantages, but LT4 replacement therapy could prevent abnormalities related to GH–IGF axis in patients with subclinical hypothyroidism.     

男性垂体催乳素大腺瘤103例临床分析

目的　探讨男性催乳素大腺瘤的临床特点、治疗方法与疗效的关系以及预后因素。方法　回顾性分析103例男性催乳素大腺瘤患者临床特点、不同治疗方式对治疗效果的影响,并初步探讨影响预后因素。结果　(1)男性催乳素大腺瘤最常见的症状是性欲或性功能减退,其次是头痛和视力减退。(2)药物治疗的患者57 8% 达到完全缓解,而单纯手术治疗仅有5 7%的患者完全缓解(P<0 001)。手术治疗不能完全缓解的患者采取药物、放疗以及两者联合治疗, 3种治疗的疗效差异无统计学意义(P=0 498)。(3)肿瘤存在侵袭性的患者较无侵袭性的患者预后差(P=0 03), 疗效不同的患者在年龄、病程、肿瘤大小、治疗前血催乳素水平以及是否存在垂体卒中方面无明显差异。结论　男性催乳素大腺瘤应首选药物治疗。肿瘤存在侵袭性是其预后不良因素。     

A multihormonal pituitary adenoma with growth hormone and adrenocorticotropic hormone production,causing acromegaly and Cushing disease

Pituitary adenoma with growth hormone (GH) and corticotropin (ACTH) production causing apparent acromegaly and Cushing disease is extremely rare. A 45-year-old woman had a pituitary macroadenoma and severe insulin resistance. Physical examination showed a fully developed acromegaly associated with mild Cushingoid features. Serum GH, insulin-like growth factor-I, ACTH, and cortisol levels were all elevated. Hormonal loading tests resulted in GH levels increasing paradoxically in response to thyrotropin-releasing hormone (TRH), but not corticotropin-releasing hormone (CRH). A similar unexpected increase in ACTH and cortisol levels occurred in response to TRH and GH-releasing hormone. After trans-sphenoidal resection of the pituitary macroadenoma immunohistochemistry revealed the presence of either diffuse but faintly GH-positive cells or sparse but distinct ACTH-stained cells. A marked amelioration of insulin resistance was observed postoperatively. The elevated ACTH and cortisol levels should therefore be investigated by CRH and dexamethasone suppression tests for the coexistence of Cushing disease to exclude the possibility of underlying ACTH-producing tumors.     

Urinary growth hormone following exercise to assess growth hormone production in adults

OBJECTIVE The insulin stress test (IST) is the most commonly used test to assess the GH reserve in children and adults. It is a time-consuming, expensive and potentially dangerous test. We investigated whether measurement of urinary growth hormone excretion following exercise would prove a reliable method to diagnose adult GH deficiency. DESIGN Healthy volunteers underwent a standard IST to confirm normal GH secretion. Using a standardized exercise protocol on a treadmill, the urinary excretion of GH was measured. Three patients confirmed as GH deficient by an IST were exercised using the same exercise protocol and their urinary excretion of GH was measured. PATIENTS Ten healthy volunteers and three patients with hypopituitarism were evaluated. MEASUREMENTS A standard IST was performed on both healthy volunteers and patients, with measurements of plasma GH and plasma cortisol. Urinary growth hormone and urinary GH/creatinine (GH/CR) ratios were measured before and after IST. On a separate visit, healthy volunteers and patients were exercised on the treadmill with measurements of plasma GH and cortisol. Urinary GH and GH/CR ratios were measured before and after exercise. RESULTS There was at least a two-fold increase in urinary GH and GH/CR ratios following exercise in all healthy adults. By contrast, patients with GH deficiency showed no rise in urinary GH or urinary GH/CR ratios following exercise. CONCLUSIONS Measurements of urinary GH following exercise can distinguish between GH-deficient adults and healthy volunteers. Urinary GH excretion can be measured over a timed interval following exercise or can be expressed as the GH/CR ratio. This can be measured on a single sample following exercise and can be used to diagnose GH deficiency. The exercise test employed for this study is arduous. We are therefore performing further studies with a less strenuous exercise protocol with a view to designing a ‘patient-friendly’ exercise test for GH deficiency in adults.     

慢性丙型肝炎复发合并亚临床甲状腺功能减退症1例

一、病例资料 患者女性,37岁,汉族,广东籍,教师.因"发现抗-HCV阳性5年"就诊.患者2003年体检时发现"抗-HCV阳性",因肝功能正常,未予以治疗.2004年8月起用普通干扰素联合利巴韦林治疗1年,HCV RNA转阴后停药,定期复查.停药6个月出现病毒学突破,肝功能异常,此后未进行抗病毒治疗,肝功能反复.2005年10月体检时发现"脂肪肝"及"甲状腺混合性结节",均未进行特殊治疗;无特殊个人吏、家族史.     

A case of estrogen-secreting adrenocortical carcinoma with subclinical Cushing's syndrome

A 25-year-old man was found to have a large right adrenal mass detected by abdominal echography and computed tomography, and presented with a mild gynecomastia. Endocrine study showed increased serum concentrations and urinary excretion of estrogens and dehydroepiandorosterone sulfate (DHEA-S). The patient had no Cushingoid features but autonomous cortisol secretion, compatible with the diagnosis of subclinical Cushing's syndrome. Surgical removal of the adrenal tumor led to normalization of serum and urinary excretion of estrogens and DHEA-S. Histopathological examination revealed a high-grade adrenocortical carcinoma (ACC). The disorganized expression of all the steroidogenic enzymes in individual tumor cells was demonstrated by immunohistochemical analysis, and the abundant expression of both aromatase mRNA and insulin-like growth factor (IGF)-II mRNA was shown by RT-PCR. These data suggest the excessive secretion of estrogen as well as the ineffective steroidogenesis by the adrenal tumor. This is a very rare case of estrogen-secreting ACC associated with subclinical Cushing's syndrome.     

A case of subclinical hypothyroidism developing marked pleural effusions and peripheral edema with elevated vascular endothelial growth factor

A 69-year-old woman was admitted for the treatment of marked pleural effusions and peripheral edema. Analytical studies of the pleural effusion revealed exudates. Culture for bacterial organisms and tuberculosis were negative, and cytology was normal. She had a mediastinal tumor at the age of 61 and regular follow-up showed no evidence of malignancy. She underwent the mediastinal tumor resection, because we thought this was the cause of her symptoms. However, her clinical symptoms persisted after surgery. Next, we noticed subclinical hypothyroidism, in which serum TSH level was elevated with concomitant normal thyroid hormone levels. In addition, serum vascular endothelial growth factor (VEGF) levels, which have been reported to be related to the pathophysiology of the extravascular volume overload, were elevated. Although her TSH level was slightly elevated (15.4 microU/ml), we started thyroid hormone replacement therapy. This therapy gradually ameliorated her clinical manifestation and abnormal laboratory data, including elevated VEGF levels. These observations indicate that even subclinical hypothyroidism may cause severe clinical manifestations. Furthermore, elevated VEGF may be a contributing factor in the pathogenesis of extravascular volume overload in hypothyroid patients.     

A case of sparsely granulated growth hormone cell adenoma associated with lymphocytic hypophysitis.

Lymphocytic hypophysitis is in itself rare and usually occurs in the postpartum period or the last trimester of pregnancy. It has not been described in combination with a pituitary tumor. A twenty-two year old woman, who had never been pregnant, presented with a history of nine months amenorrhea and spontaneous galactorrhea. She was not taking any medication and had never used oral contraceptives. Physical examination was unremarkable except that whitish fluid could be expressed from both breasts. Her visual fields were normal. Her serum PRL levels was high at 105.7 micrograms/l and increased to 138.4 micrograms/l at 60 minutes in a triple bolus test. GH values were normal and there was no evidence of overproduction of other pituitary hormones. CT scan showed an intrasellar mass with suprasellar extension. A tumor was selectively removed transsphenoidally. Morphologic examination revealed a clinically silent sparsely granulated growth hormone cell adenoma with lymphocytic infiltration of the adjacent pituitary tissue. Postoperatively her menstrual periods resumed and she conceived despite a slightly elevated PRL level. Three months after an uneventful pregnancy and full term delivery her PRL level was 69.9 micrograms/l and increased to 102.2 micrograms/l at 60 min. Basal GH and cortisol levels were normal. She remains well without replacement fourteen months after delivery. This case is of interest because it is the first reported simultaneous occurrence of a pituitary adenoma and lymphocytic hypophysitis and also because the hypophysitis preceded her first pregnancy.     

A case of macroprolactinoma encasing an internal carotid artery aneurysm,presenting as pituitary apoplexy

We present the first case of successful non-surgical treatment of an internal carotid aneurysm, embedded within a macroprolactinoma. A 53 year old male, with a previous history of Non-Hodgkin's Lymphoma (NHL), presented with severe right sided frontal headache, decreased visual acuity, and ophthalmolplegia due to a third nerve palsy. A CT scan showed a 4.6 by 4.8 cm mass in the pituitary fossa with bony erosion. Initially, it was thought to be a cerebral recurrence of the Non-Hodgkin's disease. Direst questioning revealed a long history of erectile dysfunction with loss of libido. Prolactin at presentation was 537, 200 mU/l and a diagnosis of macroprolactinoma, with apoplexy was made. A subsequent MRI brain confirmed a large macroadenoma with an intra cavernous aneurysm encased by the tumour. A therapeutic dilemma ensued due to the need for urgent decompression of the visual pathways, preferably by surgery. However, in the presence of an intrasellar aneurysm, surgery would have been extremely hazardous. The patient was therefore commenced on cabergoline and rapidly titrated up to 4 mg per week. The aneurysm was treated by endovascular occlusion of the right carotid artery under radiological control. The combination of these therapies, without conventional surgical intervention, resulted in resolution of the third nerve palsy and recovery of visual acuity in the left eye. The diagnosis and management of this condition was challenging and the final outcome, with non-surgical treatment and carotid artery occlusion was satisfactory.     

Treatment of radiation-induced growth hormone deficiency with growth hormone-releasing hormone

In children with hypothalamic causes for GH deficiency there are theoretical reasons why a GHRH analogue might be better than conventional GH therapy in promoting growth. OBJECTIVEWe have aimed to determine the efficacy and safety of growth hormone-releasing hormone (GHRH) (1–29)-NH₂ given as a twice daily subcutaneous injection in the treatment of growth failure in children with radiation-induced GH deficiency. DESIGNA multicentre study comparing growth before and after 1 year of treatment with GHRH (1–29)-NH₂, 15 μg/kg twice daily, by subcutaneous injection in children with radiation-induced GH deficiency. On completion of the study year all children were treated with GH (05 U/kg/week) and growth parameters were documented over the next year. PATIENTSNine children (six boys) with radiation-induced GH deficiency following cranial (n = 4) or craniospinal (n = 5) irradiation for a brain tumour distant from the hypothalamic–pituitary axis (n = 8) or prophylaxis against central nervous system leukaemia (n = 1) were studied. All were prepubertal when the study commenced, which was at least 2 years from radiotherapy. MEASUREMENTSAnthropometry and pubertal staging were carried out at 3-monthly intervals and bone age estimations at 6-monthly intervals (TW2 method). Pretreatment standing height velocities were compared with values during the year of GHRH treatment and then after the first year of GH therapy. In those that had received craniospinal irradiation, a change in leg-length Standard deviation score (SDS) was noted before and after GHRH therapy. Changes in skin-fold thickness and bone age during the GHRH study year were documented. Adverse events and 3-monthly measurements of clinical chemistry, haematology, lipid profile and thyroid function were recorded. RESULTSThere was a significant increase in height velocity from 33 (SD 11) cm/year before treatment, to 60 (SDS 15) cm/year after 1 year of GHRH treatment (P = 0004). GHRH maintained or improved the leg length SDS in children who had received craniospinal irradiation. Bone age increased by a mean of 11 years/chronological year during treatment with GHRH. Subsequent height velocity during 1 year of GH therapy was 75 (SD 15) cm/year. No adverse changes in biochemical or hormonal analyses were noted or adverse events that could be attributed to GHRH therapy. One child went into puberty during the GHRH study year and three were pubertal during the first year of GH therapy. CONCLUSIONIn cranially irradiated children, GHRH was effective in increasing growth velocity but this was less than that seen in response to GH therapy, although it matched that in children with isolated idiopathic GH deficiency treated with the same dose and schedule of GHRH administration.     

Development and characterization of a variant GC cell line with L-triiodothyronine-independent growth and growth hormone production

To facilitate studies of cell growth regulation by T3, we developed a variant GC cell line (V-GC) characterized by normal growth in T3-depleted (-T3) medium. The doubling time (dt) of V-GC cells was 28.8 h (-T3) and 28.0 h (+0.2 nM T3), respectively, whereas the dt of the parent GC cells, 24.0 h (+0.2 nM T3), increased to more than 100 h (-T3). The dt of V-GC cell was unaffected even by maximal T3 (5 nM). Cell protein (micrograms) per microgram DNA increased in GC cells in a T3 concentration-dependent manner, whereas V-GC cell protein was unaffected by T3. GH production appeared partially independent of T3 in V-GC cells. GH production (nanograms per 10(6)/h) in V-GC cells maintained for 3 months in -T3 medium was 3.3- to 4.6-fold greater than that in GC cells after 4 days in -T3 medium (P less than 0.001). Addition of T3 resulted in similar maximal GH production in both cell lines. The binding capacity and Ka of nuclear T3 receptors were similar in GC and V-GC cultures, and receptor down-regulation in response to added T3 occurred similarly in both cultures. Lastly, studies employing conditioned medium indicated that T3-independent growth of V-GC cells did not result from production of an autocrine growth factor. Our findings raise the possibility that overexpression of a transacting cell-specific gene-regulating protein that variably affects thyroid hormone-dependent genes may account for the phenotype of the V-GC cultures.