Endocrine Abstracts

We present the case of a 32-year-old gentleman who was initially referred to the urologists with erectile dysfunction, low libido and infertility. There was no history of headache, visual difficulty, galactorrhea and his smell sensation was fine. Blood tests done in February 2007 showed normal renal, liver and thyroid function. His Prolactin was elevated at 3086 mU/l, with no detectable macroprolactin. He had hypogonadotrophic hypogonadism (testosterone=1.8 nmol/l (10–40)...

Background: Insulin-induced hypoglycaemia (ITT) is considered the gold standard method for the evaluation of the hypothalamo-pituitary-adrenal axis. The standard short Synacthen test (SST) has been proposed as an alternative, but it may be associated with falsely reassuring results and potentially serious sequelae.Aim: To compare the serum cortisol response achieved in the SST with the one obtained during the ITT in patients with hypothalamo-pituitary di...

A 34-year-old male presented in March 2006 to the eye department with reduced visual acuity in left eye over 2 months and was initially diagnosed as retrobulbar neuritis. His vision was not improving in the next 2 months and so an MRI of the optic nerve was arranged which revealed a pituitary tumour impinging on the optic chiasma and his visual fields showed an early bitemporal hemianopia. Initial bloods revealed T4 13.5 pmol/l, TSH 1.4 μ/l, cortisol 305 nmol/l, prolactin...

A 43-year-old man presented with aching legs, gynaecomastia, erectile dysfunction, central obesity, and generalised hair loss. Examination confirmed these findings as well as showing him to be hypertensive at 160/100 mmHg. Routine haematology and biochemistry as well as levels of anterior pituitary hormones were normal, except for an inappropriately low TSH in the face of normal T3 and T4 levels. A pituitary MRI showed the presence of an ill defined area of reduced signal inte...

Context: Exogenous oestrogen administration causes prolactinoma formation in rats and there are anecdotal reports of oestrogen treatment and prolactinoma formation in gender reassignment males to females. It remains unclear whether chronic exposure to high dose oestrogen in women is linked with prolactinoma development.Aim: The aim of this study was to determine the effect of high dose subcutaneous estrogen on prolactin and gonadotrophin levels of 101 wo...

Introduction: Recent trials suggest that using ergot-derived dopamine agonists such as cabergoline in the treatment of Parkinson’s disease is associated with an increased risk of valvular heart disease. However, the dose of cabergoline used to treat hyperprolactinaemia is considerably less than that used in Parkinson’s disease.Study design: A cross-sectional study; forty four patients, who received cabergoline for at least 6 months, underwent t...

A 16-years old boy was referred for endocrine assessment of growth retardation. He had normal growth to age 7 years (tallest in his class) following which he sustained frontal head injury and subsequently exhibited growth retardation. There was no other confounding history. At age 16, height=1.47 m (below 3rd centile; mid-parental height=1.77 m), BMI=21, he was pre-pubertal. Full blood count, biochemistry and chest X-ray were unremarkable. He was 3 years behind in bone age, ha...

We report the use of Gamma knife radiosurgery (GK) to 15 somatotroph adenomas. Eight patients had refractory acromegaly despite maximal conventional treatments: all had undergone conventional radiotherapy (CRT), mean interval between CRT and GK 15.6 years. Six had undergone surgery, two on more than one occasion. Five were receiving somatostatin analog therapy, one was receiving dopamine agonist therapy, one was on pegvisomant alone. All had radiologically defined disease, wel...

Central diabetes insipidus (CDI) is an uncommon disorder characterised by a deficiency of arginine vasopressin. There are many causes of CDI including traumatic, infiltrative, inflammatory and neoplastic disorders of the pituitary or hypothalamus. CDI may be associated with a pituitary stalk lesion or thickening. Such thickening is commonly related to lymphocytic infundibular hypophysitis (LIH) or other granulomatous infiltrative disorders.We present a s...

It is unclear why GHD is associated with a reduced quality of life. Previous studies of GHD have shown impaired cardiovascular function and an increased cardiovascular mortality. We investigated whether the reduced quality of life is correlated with cardiac function and levels of cardiorespiratory fitness.Eighteen adults (9 male) with severe, untreated, GHD were studied. Cardiac power and cardiorespiratory fitness were investigated using a new, non-invas...

A 57-year lady with a history of hypertension for which she was taking bendroflumethiazide and ramipril presented with a 1 week history of worsening frontal headache and vomiting. Twenty-four hours prior to admission she became confused, had photophobia, slurred speech and was unsteady. On examination she had a Glasgow coma score of 12, was apyrexial, normotensive, tachycardic and confused. Fundoscopy was normal. There was no neck stiffness and no cranial nerve palsies. Initia...

Objective: We describe a patient who was dealt as a case of polycystic syndrome for about a decade before it was discovered that she was suffering from Cushing’s syndrome because of anterior pituitary adenoma. Our aim is to highlight the fact that even today PCOS ought to be a diagnosis of exclusion and it is vital to rule out other causes with similar features.Case report: Our patient is a 45 years old female who was levelled as a case of PCOS 10 y...

An 82-year-old man presented with weight loss and lethargy. Thyroid function tests showed a fT4 7.6 pmol/l and TSH 0.08 mU/l. Short synacthen test confirmed hypoadrenalism with baseline cortisol of 34 nmol/l and 30 min sample 156 nmol/l. He had low gonadotrphin levels and Prolactin was 551 μ/l. He was commenced on hydrocortisone and levothyroxine treatment with symptomatic improvement. An urgent CT scan revealed multiple enlarged lymph nodes above and below the diaphragm ...

A 36-year-old man was referred to the neurologists for leg weakness and pain, fatigue and lethargy for 2 years. Sarcoidosis was diagnosed 6 years previously, on the basis of uveitis, lower motor neurone facial palsy, hilar lymphadenopathy and transbronchial biopsy. Prednisolone had been discontinued 3 years prior to his current presentation.His blood pressure was 99/71. Examination was otherwise unremarkable. His ACE was 109 U/l (10–70). His TSH was...

Background: Pituitary adenomas (PA) have traditionally been considered as very rare conditions, with an estimated prevalence of 25 cases/100 000 inhabitants. However, these data have been extracted either from cancer registries or from hospital databases and therefore, may not be accurate.Aim: To ascertain the prevalence of PA and the characteristics of the patients diagnosed with them in a large population of inhabitants.Methods: ...

Pituitary apoplexy (characterised by sudden onset headache, meningism and cranial nerve defects) is an unusual but serious complication of pituitary macroadenoma. Less than 2 percent of patients with pituitary macroadenoma present initially with apoplexy. Pituitary adenoma is the presenting feature in 10–25% of cases with multiple endocrine neoplasia (MEN) type 1, with microadenomas accounting for 2/3 of MEN-related pituitary adenomas.A 35-year-old ...

Acromegalic congestive cardiac failure (CCF) is a serious and late complication of untreated acromegaly with associated high morbidity and mortality.1 Spontaneous recovery of end stage acromegalic CCF following autoinfarction of a somatotroph adenoma has not been previously reported.We report the case of a 61-year-old woman who presented with features of severe biventricular CCF and an acromegalic phenotype. Echocardiography revealed poor LV f...

Recent literature suggests anterior pituitary hormone deficiency (APHD) is common in paediatric patients with idiopathic cranial diabetes insipidus (CDI); this has been attributed to autoimmune panhypopituitarism.1 We therefore determined the frequency of coexisting APHD and autoimmune disease in our cohort of patients with idiopathic adult CDI.Eight patients with idiopathic CDI were reviewed (6 females mean age at diagnosis 30 years, range 7&...

Aims: There is a lack of literature about mental and emotional dysfunction in patients with acromegaly or other pituitary tumours although impaired quality of life is well recognised. We examined whether adult patients with acromegaly experience a lower quality of life (QoL) than adult patients with other pituitary tumours and whether any difference in QoL is attributable to the patient’s perceived body image.Methods: Medical records were used to id...

Differentiation between non functioning pituitary macroadenomas (NFPA) and prolactinomas may be difficult as hyperprolactinaemia can also be present at diagnosis in NFPA cases due to pituitary stalk compression (disconnection hyperprolactinaemia). Some authors suggested that prolactin >2,000 mIU/l is almost diagnostic of a prolactinoma, while others use a higher cut-off of >5000 mIU/l. Our aim was to identify the level of prolactin above which a prolactinoma was more l...

Studies on the probability of recurrence of surgically treated but radiotherapy (RT) naïve non-functioning pituitary adenomas (NFPA) are inconsistent and selective as cases deemed to be at high risk of recurrence were prophylactically irradiated. We traditionally used very low rate of post-operative RT leaving us with a largely unselected cohort.We identified 223 surgically resected, histology-proven NFPA cases. Only 9% received post-operative RT an...

Back ground: Pituitary adenomas are the most common cause of a mass in the sella, accounting for up to 10–15% of intracranial neoplasm’s1. However, when dealing with abnormal intrasellar masses, a number of different etiologies are possible: germ cell tumour, metastatic tumours, granulomatous, and inflammatory processes2. We report an unusual case of primary pituitary lymphoma diagnosed on biopsy presenting as panhypopituitarism and Diabetes Ins...

Introduction: POMC is activated in ACTH-dependent Cushing’s Syndrome. We have previously shown that RNA interference (RNAi) targeting POMC coding and promoter sequences induces silencing of POMC and a reduction in ACTH. We have modified our most potent exonic sequence with locked nucleic acid (LNA) chemistry. This is purported to increase serum stability. Here we test whether the LNA confers stability without compromising siRNA silencing potency.<...

Annexin 1 (ANXA1) externalised from folliculostellate cells is known to be an essential intermediate in the early delayed (30 min- 3 h) negative feedback of glucocorticoids on the release of ACTH and other pituitary hormones. We have used a well-characterised folliculostellate cell line (TtT/GF cells) to investigate the mechanism by which ANXA1, a cytoplasmic protein, is externalised by cells. Externalisation is stimulated by dexamethasone (Dex) and inhibited by inhibitors of ...

Initial clinical trials with pegvisomant at doses of up to 80 mg once weekly led to a 30% fall in IGF-I. Subsequently, daily administration of up to 40 mg/day (280 mg/week) achieved an IGF-I within reference range in 97% of patients. Pegvisomant’s half-life is >70 h suggesting weekly dosing may be possible using higher doses than in the original trials.We performed a two-centre, open-label prospective study in seven patients (4M, 3F, mean age 57...

The pathogenesis of gonadotrophin secreting pituitary tumours (gonadotrophinomas) remains poorly understood. BMP2, known to be important in the control of cell proliferation and differentiation, is essential for commitment of undifferentiated pituitary cells to the gonadotroph cell lineage. Attenuation of its expression is critical in allowing terminal differentiation. BMPs are associated with up-regulated expression of Id (Inhibitors of differentiation) proteins with predicte...

Adult GH deficiency is associated with poor quality of life (QoL) which has been shown to improve with GH replacement is some but not all, mainly short-term studies. In addition, it remains unclear whether this improvement in QoL is sustainable.We aimed to establish the short and long-term effect of GH replacement on QoL in 167 adult patients with severe GH deficiency in a prospective study. QoL was assessed using the quality of life-assessment of growth...

Introduction: Lymphocytic hypophysitis is a rare inflammatory disease of the pituitary gland. The aetiology is unknown though probably of autoimmune origin. This condition usually occurs in women during pregnancy or in the post partum period. Recurrent disease in pregnancy is rare.Case report: We present a 35-year-old patient of African origin who initially presented in 2004 at 12 weeks gestation with headaches, a third nerve palsy but no visual f...

Background: Recent studies have indicated that macroprolactinaemia accounts for up to 26% of biochemical hyperprolactinaemia depending on the assay in use. Delayed metabolic clearance of macroprolactin together with detection by most automated prolactin immunoassay systems leads to pseudo-hyperprolactinemia in patients harbouring this form of complexed prolactin.We here describe the use of serial macroprolactin measurement to assist in the management of ...

Background: Pleuro-pulmonary inflammatory fibrotic syndrome is a rare but recognised complication of dopamine agonist (DA) therapy in Parkinson’s disease. Here, we describe a case of asymptomatic pulmonary fibrosis, presumed secondary to DA therapy, in a patient treated with cabergoline for an invasive macroprolactinoma.Case report: A 47-year-old previously fit man was admitted as an emergency with a 3 days history of headache followed by collapse. ...

Context: We have previously demonstrated that, in cranially irradiated patients with normal peak GH responses to both the insulin tolerance test (ITT) and the growth hormone-releasing hormone plus arginine stimulation test (GHRH+AST), somatotroph reserve can be substantially reduced, while individual and overall spontaneous GH secretion remain entirely normal due presumably to a compensatory increase in hypothalamic stimulatory input within a partially damaged hypothalamic pit...

A 41-year-old woman presented to her optician 3 weeks post-partum with frontal headaches and visual blurring. On examination, a bitemporal hemianopia was found.She had previously been under our care with autoimmune hypothyroidism diagnosed 3 years earlier on the basis of symptoms and confirmatory biochemistry – TSH 10.9 mU/l, T4 10.6 pmol/l, TPO 66 (<50). This had been adequately replaced throughout pregnancy, which had been uneventful until the...

Background: Adult hypopituitarism is associated with premature vascular mortality for which the underlying mechanisms are unknown but untreated GH deficiency is proposed as a potential contributor.Objectives: To characterise vascular risk, including paraoxonase-1 (PON1; an antioxidant enzyme which preserves LDL against oxidation), in adults with treated panhypopituitarism.Study subjects: The study had full ethics approval. Data are...

Some patients with Cushing’s have only periodic hypercortisolism, known as cyclical Cushing’s, becoming eucortisolaemic or even transiently subnormal between periods of hypercortisolaemia. We report two cases and discuss the management.A 23-year-old lady presented in March 2007 with Cushingoid features. Initial urinary free cortisol was raised at 594 nmol/l. A midnight cortisol of 568 nmol/l and post-48 h low dose dexamethasone cortisol of 351 ...

Pituitary infarctions are not unknown in patients with pituitary tumours. We describe here a 39-year-old lady, who presented with a history of sudden onset severe headache without any restriction of her visual fields. She had features of acromegaly with enlarged hand and feet size, progressive deepening of her voice and coarsening of facial features over the preceding year. She also had a euthyroid multinodular goitre. CT scan and MRI of the pituitary gland suggested cystic de...

Iron deficiency anemia (IDA) is the most pervasive of all nutritional deficiencies and is considered very serious during pregnancy, with deleterious consequences for both the mother and her developing fetus. The female albino rats of Wistar strain were fed on iron deficient diets (30, 15, 7 and 2 mgFe/kg of diet) and control diets (50 mgFe/kg of diet). Prior to one month of mating the females were anaesthetised by ether and the tail blood was collected for the evaluation of bl...

A 45-year-old professional jockey presented as an emergency with a 10 day history of polyuria and polydipsia in excess of 10 l daily. 10 days previously he had suffered a head injury complicated by concussion while horse racing in Norway. There was no significant past medical or drug history but he admitted to the use of ‘wasting’ methods prior to a race to maintain his body weight. Examination was unremarkable. Renal function, liver function, thyroid function, serum...

Pituitary carcinoma is rare and diagnosis requires demonstration of cerebrospinal and/or systemic metastasis. We present case of a 64-year-old lady who presented with widespread spinal metastasis from a pituitary adenoma diagnosed 36 years ago. Our patient presented in 1971 with visual failure, headache and oligomenorrhoea. Imaging confirmed pituitary macroadenoma and she underwent transcranial hypophysectomy. Histology revealed chromophobe adenoma. Post operatively her vision...

Background: In most people, prolactin circulates predominantly as a 23-kDa monomer, and a high-molecular-weight form which in the vast majority of cases consists of a complex of prolactin and an anti-prolactin IgG autoantibody, commonly referred to as macroprolactin. This cross-reacts with conventional laboratory assays for prolactin.Report: In a consecutive series of 218 patients with prolactin elevated to 400 μ/l or more in men (normal range &#880...

Background: Endoscopic endonasal transsphenoidal hypophysectomy is an alternative to microscopic transsphenoidal hypophysectomy. The technique may provide a safer, quicker and more effective treatment.Objectives: To assess preliminary results of this technique when introduced at a single centre with a single surgeon.Methods: A retrospective analysis of 62 patients who underwent transsphenoidal surgery, 33 microscopic and 29 endosco...

Background and aims: Diabetes insipidus (DI) is a common complication after transsphenoidal surgery (TSS), but resolves in the majority of patients. We determined the osmolalities and timing of DI most that best predicted long-term outcome.Methods: Case series study randomly including 54 patients out of total 99 patients who underwent transsphenoidal surgery over 18 months. Follow up information was ascertained from clinic review or by telephone intervie...

A 30-year-old female presented to accident and emergency having been found collapsed. The patient had a reduced Glasgow Coma Scale of 10, was pyrexial, clinically in shock and pale in colour. Initial investigations confirmed hypoglycemia and a metabolic acidosis. A collateral history described a 3 days history of diarrhoea. Her 5-year-old child (who was conceived normally) also had diarrhoea.The impression was of shock secondary to sepsis and hypovolemia...

This 55-year-old gentleman presented to endocrine clinic following an episode of septicaemic shock complicating benign prostatic surgery one year previously. He subsequently developed symptoms of lethargy, palpitations, lightheadedness, peripheral weakness and loss of libido, which had developed after this episode. Routine biochemistry and ambulatory electrocardiography measurements were normal.Endocrine testing revealed:: - Undetectable gonadotrophins (...

Introduction: Although current medical therapies for acromegaly are highly effective, 30% of patients are left with inadequately controlled growth hormone (GH) levels. To investigate a novel therapeutic strategy we have used RNA interference (RNAi) to target GH coding and promoter sequences in vitro and assessed the effect on gene expression and DNA methylation.Method: A careful bioinformatics approach revealed only one area in the coding sequence...

The aim of treatment in patients with acromegaly is to achieve serum GH/ IGF-I concentrations associated with cure or normalisation of mortality. Using the West Midlands acromegaly database (n=501) we assessed a number of parameters in the follow up of patients with acromegaly including the reliability of basal fasting GH in predicting nadir or mean GH during oral glucose tolerance test (OGTT) or growth hormone day curve (GHDC) respectively, the degree of discordance be...

Objective: There is little data on suprasellar meningiomas regarding their effect on pituitary hormones and outcome following surgical intervention.Methods: In a database of patients undergoing surgical treatment for a pituitary mass set up in 1997, all cases of histologically proven meningioma were identified. Medical records were reviewed in order to determine menigioma site, size, pre- and postoperative vision as well as pre- and postoperative pituita...

Acromegaly is associated with increased morbidity and mortality. There are several treatment options for acromegaly including surgery, radiotherapy and medical therapy. The aims of treatment in patients with acromegaly is to achieve GH and IGF-I concentrations associated with cure or normalisation of mortality.We examined predictive factors of response to treatment with dopamine agonists (DA) and somatostatin analogues (SSA) in a cohort of 501 patients w...

Acromegaly is associated with increased morbidity and premature mortality which has been demonstrated in a number of retrospective studies reporting a standardised mortality ratio (SMR) between 1.3 and 3. Many patients with acromegaly develop hypopituitarism as a result of the pituitary adenoma itself or surgery and/or radiotherapy. Hypopituitarism is also associated with an increased SMR (1.2–2.17).Using the West Midlands Acromegaly database (n<...

Particulate guanylyl cyclases are expressed in all endocrine organs and serve as specific receptors of the natriuretic peptides ANP, BNP and CNP. Guanylyl cyclase-B (GC-B/Npr2) receptors specifically mediate the biological effects of CNP in its target tissues. Targeted disruption of either CNP or GC-B results in pituitary growth hormone deficiency and dwarfism as a result of achondroplasia. Despite this, molecular regulation of GC-B expression is poorly elucidated. Therefore, ...

Introduction: We present the outcome for the first 21 patients undergoing neuronavigation–guided, endoscopic transphenoidal surgery for pituitary dependent Cushing’s disease in our centre since August 2001. All operations were consecutive, and undertaken by the same neurosurgeon and endoscopic nasal surgeon.Methods: Records are available for 20 cases. Pre and post operative management of cases was led by the endocrine team with standard assessm...

CNP, the third peptide of the mammalian natriuretic peptide family, exerts its biological effects through activation of the guanylyl cyclase B (GC-B) receptor and resulting cGMP accumulation. Our previous studies reported that CNP stimulates phosphorylation of MAPK family proteins in GH3 somatotrophs. This present study aimed to further characterise the mechanism of CNP-stimulated ERK phosphorylation and resulting biological consequences in GH3 cells. Western blot analyses sho...

The propensity for prolactin (PRL) to form high molecular mass complexes in serum is well described. Macroprolactin (mPRL), a PRL-immunoglobulin complex (>100 kDa), is the predominant form of PRL in up to 20% of patients with hyperprolactinaemia. Big PRL (bPRL, 40–50 kDa) is a ubiquitous, minor component of serum PRL rarely the major immunoreactive form, the nature of which is unclear. Using gel filtration chromatography (GFC) we have investigated the relative abundan...

Dynamic pituitary testing is a time consuming and high cost investigation. For effective use of this procedure a close audit of the effectiveness and outcome of testing is required. At UCH we have developed a streamlined nurse led service with medical supervision and we now present an audit of 1 year of testing.Forty-one patients underwent pituitary function testing for growth hormone (GH) and ACTH during 2006. Referral source was from the endocrine team...

Background: Surgery, sometimes supported by adjunctive radiotherapy (RT), is the treatment of choice for patients with non-functioning pituitary adenoma (NFA). Previous studies have shown that patients treated with pituitary RT have doubling of mortality ratio due to cerebrovascular disease (CVD) but the reason for this excess is unclear. Transcranial Doppler (TCD) can be used to measure blood velocity in the middle cerebral arteries (MCAs) within the circle of Willis and also...

Nelson’s syndrome is a recognised complication of bilateral adrenalectomy for Cushing’s disease. The treatment of this condition can be extremely difficult. We report a case who failed to respond to traditional treatments, was given a novel chemotherapeutic agent temozolomide.A 50 years old lady was diagnosed with pituitary dependent Cushing’s disease in 1998. She underwent transphenoidal hypophysectomy (TSS) twice, followed by conventiona...

Natriuretic peptides, ANP, BNP and CNP, exert the majority of their effects via particulate guanylyl cyclase receptors (GC-A or GC-B), resulting in increased cellular cGMP levels. Several studies have examined the pharmacological properties of GC-B receptors in many systems, and desensitization (tachyphylaxis, loss of response) has been reported to occur. Targeted deletion (in mice) or genetic mutations (in humans) of the GC-B receptor have been implicated in a dwarfism phenot...

Patients with GHD have an, adverse body composition, insulin resistance, atherogenic lipid profile and impaired quality of life. We undertook a single centre retrospective audit of hypopituitary adults to quantify the long-term effects of dose-titrated GH replacement.The cohort comprised 53 patients defined as severely GHD using the GST (median peak GH 2.4 μ/l). Mean age 42±16.9 years, 23F, BMI 29.3±5.3 kg/m2. GH was titrated un...

Gonadotrophs have previously been shown to be the predominant source of C-type natriuretic peptide (CNP) in the anterior pituitary, and CNP causes enhanced cGMP accumulation in αT3-1 gonadotrophs. However, the biological role of CNP in gonadotrophs remains elusive. In the current study, we examined the molecular and functional characteristics of the gonadotroph natriuretic peptide system. Using two well-characterised gonadotroph cell lines of different developmental origi...

Cranial radiotherapy is widely used in combination with chemotherapy to treat patients with primary brain tumours. Increased survival has lead to the recognition of long term sequelae, including endocrine dysfunction due to radiation-induced hypothalamic–pituitary damage. Here we assessed health-related quality of life and endocrine function in 31 adult long term survivors (median age 45, range 29–65 years; 21M, 10F) of primary brain tumours outside the hypothalamic&...

The use of the simplified IM glucagon stimulation test (IMGST) over its standard counterpart in the diagnosis of GH and cortisol deficiency has been advocated. Despite apparent comparable diagnostic utility, the simplified IMGST is capable of producing false positive results, raising the potential for misdiagnosis if relied upon exclusively.The aim of this study was to re-evaluate the diagnostic utility of the two forms of the IMGST, ascertaining the mag...

The diagnosis of Cushing’s syndrome (CS) remains a major clinical challenge especially in a proportion of patients that have discordant results in the available tests. Although the measurement of 24-h urine free cortisol (UFC) is a useful test for the diagnosis of CS, 10–15% of patients have at least one measurement within the normal range and multiple measurements may be required in order to raise its sensitivity. In this study we sought to evaluate the value of the...

We describe the case of an Asian male who is currently 20 years of age. He originally presented aged 18 months with short stature (height below 3rd centile). Isolated growth hormone (GH) deficiency was confirmed by an insulin tolerance test (normal thyroid function/cortisol/GH antibodies). He commenced GH injections (1 unit/day), to which he responded well, reaching the 50th centile for height within one year. Due to his parents’ wishes, GH therapy was discontinued at 3 y...