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Biomedical subjects

Amar Agha

Publications and source records attributed to Amar Agha.

16 recordsLinked to original sources
PubMed2007

Unmasking of central hypothyroidism following growth hormone replacement in adult hypopituitary patients.

BACKGROUND: The effect of GH replacement on thyroid function in hypopituitary patients has hitherto been studied in small groups of children and adults with conflicting results. OBJECTIVE: We aimed to define the effect and clinical significance of adult GH replacement on thyroid status in a large cohort of GH-deficient patients. PATIENTS AND METHOD: We studied 243 patients with severe GH deficiency due to various hypothalamo-pituitary disorders. Before GH treatment, 159 patients had treated central hypothyroidism (treated group) while 84 patients were considered euthyroid (untreated group). GH dose was titrated over 3 months to achieve serum IGF-1 concentration in the upper half of the age-adjusted normal range. Serial measurements of serum T4, T3, TSH and quality of life were made at baseline and at 3 and 6 months after commencing GH replacement. RESULTS: In the untreated group, we observed a significant reduction in serum T4 concentration without a significant increase in serum T3 or TSH concentration; 30/84 patients (36%) became hypothyroid and needed initiation of T4 therapy. Similar but lesser changes were seen in the treated group, 25 of whom (16%) required an increase in T4 dose. Patients who became hypothyroid after GH replacement had lower baseline serum T4 concentration, were more likely to have multiple pituitary hormone deficiencies and showed less improvement in quality of life compared with patients who remained euthyroid. CONCLUSION: GH deficiency masks central hypothyroidism in a significant proportion of hypopituitary patients and this is exposed after GH replacement. We recommend that hypopituitary patients with GH deficiency and low normal serum T4 concentration should be considered for T4 replacement prior to commencement of GH in order to provide a robust baseline from which to judge the clinical effects of GH replacement.

Adolescent↗
PubMed2006

The incidence and pathophysiology of hyponatraemia after subarachnoid haemorrhage.

BACKGROUND: Hyponatraemia is common following subarachnoid haemorrhage (SAH) but the pathogenesis is unclear. Objective To establish the incidence, pathophysiology and consequences of hyponatraemia following SAH. METHODS: A retrospective case-note analysis of all patients with SAH admitted to Beaumont Hospital between January 2002 and September 2003. Three hundred and sixteen cases of SAH were substantiated by computed tomography (CT) scan and angiogram findings. Hyponatraemia was defined as plasma sodium < 135 mmol/l. RESULTS: One hundred and seventy-nine patients (56.6%) developed hyponatraemia and 62 (19.6%) developed significant hyponatraemia (plasma sodium < 130 mmol/l). The incidence of severe hyponatraemia following hypophysectomy was lower in the period of analysis (5/81, 6.2%, P < 0.01). Hyponatraemia was more common in patients with identified aneurysms (anterior circulation 102/168, 60.7%, posterior circulation 56/95, 60.8%) than in those with no radiological aneurysm (21/54, 38.8%, P < 0.001). Hyponatraemia was more common after aneurysmal clipping (68/103, 66%) or coiling (82/132, 62%) than after conservative treatment (29/81, 36%, P < 0.001). The aetiology of significant hyponatraemia was the syndrome of inappropriate antidiuretic hormone secretion (SIADH) 39/62 (69.2%), cerebral salt-wasting syndrome (CSWS) 4/62 (6.5%), hypovolaemic hyponatraemia 13/62 (21%), hypervolaemic hyponatraemia 3/62 (4.8%) and mixed CSW/SIADH 3/62 (4.8%). Hyponatraemia was associated with longer hospital stay (24.0 +/- 2.6 vs. 11.8 +/- 0.8 days, P < 0.001) but did not affect mortality (P = 0.07). Hyponatraemia developed more than 7 days following SAH in 21.4% and more then 7 days following intervention in 31.8%. CONCLUSIONS: Hyponatraemia is common following SAH and is associated with longer hospital stay. Clipping and coiling of aneurysms are associated with higher rates of hyponatraemia. SIADH is the commonest cause of hyponatraemia after SAH. Delayed hyponatraemia is common, and has implications for early discharge strategies.

Adolescent↗
PubMed2006

Anterior pituitary dysfunction following traumatic brain injury (TBI).

Traumatic brain injury (TBI) is the commonest cause of death and disability in young adults living in industrialized countries. Several recent studies have convincingly shown that anterior hypopituitarism is a common complication of head trauma with a prevalence of at least 25% among long-term survivors. This is a much higher frequency than previously thought and suggests that most cases of post-traumatic hypopituitarism (PTHP) remain undiagnosed and untreated. These findings raise important questions about the potential contribution of PTHP to the high physical and neuropsychiatric morbidity seen in this group of patients. In this review, we examine the published reports on the neuroendocrine abnormalities in TBI patients and highlight new data that give novel insights into the natural history of this disorder. We discuss the potential contribution of PTHP to recovery and rehabilitation after injury and the need for the identification and the appropriate and timely management of hormone deficiencies to optimize patient recovery from head trauma, improve quality of life and avoid the long-term adverse consequences of untreated hypopituitarism.

Adult↗
PubMed2005

The long-term predictive accuracy of the short synacthen (corticotropin) stimulation test for assessment of the hypothalamic-pituitary-adrenal axis.

CONTEXT: The high-dose short Synacthen (corticotropin) test (SST) is widely used to investigate suspected secondary adrenal insufficiency, but concern remains about falsely reassuring results. OBJECTIVE: Our objective was to evaluate the long-term safety of the SST. METHOD: We retrospectively evaluated the clinical outcome in 178 patients who achieved 30-min cortisol values in the lowest 15th percentile of normal healthy responses. Thirty patients were later excluded because of missing case notes (20 patients) or unsubstantiated pituitary pathology (10 patients). The remaining 148 patients were divided into two groups: group 1, patients with cortisol response between the 5th and 15th percentiles of normal response (551-635 nmol/liter, 98 patients); and group 2, patients with borderline response between the 2.5th and 5th percentiles (510-550 nmol/liter, 50 patients). Patients did not receive routine glucocorticoid therapy, but those in group 2 were advised to take hydrocortisone in case of intercurrent illness. RESULTS: The median follow-up period from the initial SST was 4.2 yr (range, 4 months to 7 yr). A total of 137 patients showed no clinical or biochemical evidence of adrenal insufficiency during follow-up. Of the remaining 11 patients, seven became hypoadrenal after subsequent pituitary surgery or radiotherapy, one patient in group 1 developed adrenal insufficiency at 2 yr, and one patient in group 2 developed adrenal insufficiency at 6 months. The other two patients who were in group 2 had clinical diagnostic uncertainty. CONCLUSION: The high-dose SST is safe for the purpose of excluding clinically significant secondary adrenal insufficiency and is indicated as the first line of investigation for this purpose.

Adenoma↗
PubMed2005

Hypothalamic-pituitary dysfunction after irradiation of nonpituitary brain tumors in adults.

CONTEXT: Hypothalamic-pituitary (HP) dysfunction is common in children treated with cranial radiotherapy (RT) for brain tumors, but there is little known about the risk of HP dysfunction in adults treated with RT for primary nonpituitary brain tumors. OBJECTIVE: The objective was to study the frequency of HP dysfunction in adults after RT for nonpituitary brain tumors. METHOD: We studied 56 adult patients who received external beam RT for primary nonpituitary brain tumors at time intervals of 12-150 months after RT. The control group consisted of 20 RT-naive patients with primary brain tumors. GH and adrenal axes were assessed using the insulin tolerance test or the glucagon stimulation test. Gonadotroph, thyrotroph, and lactotroph function were assessed using baseline blood measurements. The biological effective dose (BED) to the HP axis was calculated in the RT patients. RESULTS: Hypopituitarism was present in 41% of patients. The frequency of GH, ACTH, gonadotropin, and TSH deficiencies, and hyperprolactinemia was 32, 21, 27, 9, and 32%, respectively. Any degree of hypopituitarism and GH deficiency was significantly associated with longer time interval from RT and greater BED. However, gonadotropin deficiency and hyperprolactinemia were only related to BED, whereas ACTH deficiency was only significantly associated with the time interval from RT. One RT-naive patient was GH deficient. CONCLUSION: Adult patients treated with cranial irradiation for primary nonpituitary brain tumors are at high risk of hypopituitarism, which is time and dose dependent. Long-term surveillance and periodic evaluation are needed. We recommend that adult late effect clinics, similar to those for children, should be established.

Adrenocorticotropic Hormone↗
PubMed2005

Small-cell lung cancer presenting as diabetes insipidus and Cushing's syndrome.

Small-cell lung cancer presenting with a combination of cranial diabetes insipidus and Cushing's syndrome secondary to ectopic adrenocorticotropin (ACTH) secretion is very rare and has only been described previously in one case report Our patient was a 49 year old man, in whom the initial presenting features of small-cell lung cancer were cranial diabetes insipidus secondary to pituitary metastases and severe hypokalaemia resulting from ectopic ACTH hormone secretion. This case is a remarkable example of the complex metabolic endocrine manifestations of small-cell lung cancer.

ACTH Syndrome, Ectopic↗
PubMed2005

High risk of hypogonadism after traumatic brain injury: clinical implications.

Several recent studies have convincingly documented a close association between traumatic brain injury (TBI) and pituitary dysfunction. Post-traumatic hypogonadism is very common in the acute post-TBI phase, though most cases recover within six to twelve months following trauma. The functional significance of early hypogonadism, which may reflect adaptation to acute illness, is not known. Hypogonadism persists, however, in 10-17% of long-term survivors. Sex steroid deficiency has implications beyond psychosexual function and fertility for survivors of TBI. Muscle weakness may impair functional recovery from trauma and osteoporosis may be exacerbated by immobility secondary to trauma. Identification and appropriate and timely management of post-traumatic hypogonadism is important in order to optimise patient recovery from head trauma, improve quality of life and avoid the long-term adverse consequences of untreated sex steroid deficiency.

Brain Injuries↗
PubMed2005

The natural history of post-traumatic hypopituitarism: implications for assessment and treatment.

PURPOSE: Hypopituitarism has been reported in up to half of long-term survivors of traumatic brain injury. We attempted to define the natural history of post-traumatic hypopituitarism to devise guidelines for the optimal timing of patients' assessment and hormone replacement. SUBJECTS AND METHODS: Fifty consecutive patients with severe or moderate head trauma were enrolled in a prospective study of pituitary function during the acute phase, at 6 months, and at 12 months after injury. Growth hormone and adrenocorticotropin hormone reserves were assessed using the glucagon stimulation test. Baseline serum concentrations of other anterior pituitary hormones were measured. Results were compared with normative data obtained from matched healthy controls. RESULTS: Nine patients (18%) had growth hormone deficiency in the acute phase; at 6 months, 5 patients recovered function and 2 new deficiencies were detected; at 12 months, 1 patient recovered, leaving 5 patients (10%) with growth hormone deficiency. Eight patients (16%) showed subnormal cortisol response in the acute phase; at 6 months, 4 patients had recovered and 5 new deficiencies were detected; all 9 patients had persistent abnormalities at 2 months. Forty patients (80%) had gonadotropin deficiency in the acute phase, of whom 29 (73%) recovered by 6 months and 34 (85%) recovered by 12 months. Thyrotropin deficiency was present in 1 patient in the acute phase, who recovered by 6 months; 1 new case was diagnosed at 6 months, which persisted at 12 months. CONCLUSION: After traumatic brain injury, early neuroendocrine abnormalities are sometimes transient, whereas late abnormalities present during the course of rehabilitation. A follow-up strategy with periodic evaluation is a necessary part of the optimal care for patients with traumatic brain injury.

Acute Disease↗
PubMed2005

Spontaneous recovery from posttraumatic hypopituitarism.

Hypopituitarism is an increasingly recognized complication of traumatic brain injury that can have significant potential to impair recovery and rehabilitation in affected survivors. Although posttraumatic cranial diabetes insipidus is known to be transient in many cases, recovery of established anterior pituitary hormone deficiency is thought to be a very rare event. We report the case of a 25-yr-old man who incurred severe traumatic brain injury in 1997. Sixteen months later, dynamic pituitary stimulation tests revealed severe growth hormone and adrenocorticotropin hormone deficiency. He was treated with recombinant human growth hormone and hydrocortisone. Five years after traumatic brain injury, repeat neuroendocrine assessment, prompted by an increasing serum insulin-like growth factor-1 level, showed normal growth hormone and adrenocorticotropin hormone responses. This is the first case report, to our knowledge, to show that adult posttraumatic growth hormone deficiency can be reversible. The recognition that anterior pituitary dysfunction can recover after traumatic brain injury has implications for the follow-up of patients with hypopituitarism secondary to head trauma to avoid unnecessary, expensive, and potentially harmful therapy.

Adrenocorticotropic Hormone↗
PubMed2005

The natural history of post-traumatic neurohypophysial dysfunction.

BACKGROUND AND OBJECTIVES: Posterior pituitary function remains poorly investigated after traumatic brain injury (TBI). We report the results of a study designed to prospectively define the natural history of post-traumatic diabetes insipidus (DI) and syndrome of inappropriate antidiuretic hormone secretion (SIADH) using standard reliable methodology. DESIGN AND METHODS: 50 consecutive patients with severe or moderate TBI (initial Glasgow Coma Scale (GCS) score 3/15-13/15) were prospectively studied on three occasions: at the acute phase and at 6 months and at 12 months following TBI. In the acute phase, DI was diagnosed either by the presence of hypernatraemia in association with hypotonic polyuria or by the water-deprivation test (WDT) and, at 6 and 12 months by the WDT in all patients. Normative data on response to the WDT were obtained from healthy matched volunteers. Functional outcome was assessed using the Glasgow Outcome Scale (GOS). RESULTS: 13 patients (26%) had DI in the acute post-TBI phase, of whom nine patients recovered by 6 months and one additional patient recovered by 12 months. Of the remaining three patients with permanent DI, two had partial vasopressin deficiency. Acute-phase peak plasma osmolality correlated negatively with the initial GCS scores (r = -0.39, P = 0.005) and with the GOS scores (r = -0.45, P = 0.001). Seven patients had SIADH in the acute phase of TBI but none did at 6 or 12 months. No new cases of DI or SIADH were noted after the acute phase. CONCLUSION: This prospective study shows that posterior pituitary dysfunction is common following TBI. Most cases recover completely but there is an appreciable frequency of long-term DI which can be subtle and should be recognized and managed appropriately.

Adolescent↗
PubMed2004

Attenuation of vasopressin-induced antidiuresis in poorly controlled type 2 diabetes.

Renal resistance to vasopressin has been demonstrated in type 1 diabetes and in type 2 diabetes with nephropathy. However, renal response to vasopressin in type 2 diabetes without nephropathy has not been studied. We studied 10 subjects with poorly controlled type 2 diabetes (PCDS; Hb A(1c) >9%), 10 subjects with well-controlled type 2 diabetes (WCDS; Hb A(1c) <7%), and 10 matched nondiabetic control subjects (NDCS) during a euglycemic 8-h water deprivation test. None of the subjects had nephropathy. Water deprivation caused similar rises in plasma vasopressin concentrations in all three groups, but the rise in urine osmolality in PCDS (280.3 +/- 49.7 to 594.4 +/- 88.5 mosmol/kgH(2)O) was lower than in WCDS (360.7 +/- 142.8 to 794.1 +/- 77.3 mosmol/kgH(2)O, P < 0.001) or NDCS (336.0 +/- 123.3 to 786.5 +/- 63.3 mosmol/kgH(2)O, P = 0.019). Total urine output was higher in the PCDS than in WCDS and NDCS (P < 0.05). Linear regression analysis showed that, in PCDS, the osmotic thresholds for thirst (291.9 +/- 4.6 mosmol/kgH(2)O) and vasopressin release (291.1 +/- 2.9 mosmol/kgH(2)O) were higher compared with WCDS (286.6 +/- 1.8 and 286.0 +/- 3.6 mosmol/kgH(2)O, respectively) and NDCS (286.0 +/- 2.4 and 284.1 +/- 4.7 mosmol/kgH(2)O, respectively) (between groups P < 0.001 for both variables). Under conditions of euglycemia, PCDS have impaired renal response to vasopressin and elevated osmotic threshold for thirst and vasopressin release in response to dehydration. Under conditions of chronic hyperglycemia, these abnormalities may significantly contribute to the development of dehydration in PCDS.

Aged↗
PubMed2004

Neuroendocrine dysfunction in the acute phase of traumatic brain injury.

BACKGROUND: Pituitary hormone abnormalities have been reported in up to 50% of survivors of traumatic brain injury (TBI) who were investigated several months or longer following the event. The frequency of pituitary dysfunction in the early post-TBI period is unknown. AIM: To evaluate the prevalence of anterior and posterior pituitary dysfunction in the early phase following TBI. SUBJECTS: Fifty consecutive patients admitted to the neurosurgical unit with severe or moderate TBI [initial Glasgow Coma Scale (GCS) score 3-13], and 31 matched healthy control volunteers were studied. METHODS: The glucagon stimulation test (GST) was performed at a median of 12 days (range 7-20) following TBI. Baseline thyroid function, PRL, IGF-1, gonadotrophins, testosterone or oestradiol, plasma sodium, plasma and urine osmolalities or the standard observed water deprivation test were performed. The control subjects underwent the GST for GH and cortisol responses; other parameters were compared to locally derived reference ranges. RESULTS: Control data indicated that peak serum GH of > 5 ng/ml and cortisol > 450 nmol/l following glucagon stimulation should be taken as normal. Nine TBI patients (18%) had GH response < 5 ng/ml (12 mU/l). Eight patients (16%) had peak cortisol responses < 450 nmol/l. Compared to controls, basal cortisol values were significantly lower in patients with subnormal cortisol responses to glucagon and significantly higher in patients with normal cortisol responses (P < 0.05). GH and cortisol deficiencies were unrelated to patient age, BMI, initial GCS or IGF-1 values (P > 0.05). Forty patients (80%) had gonadotrophin deficiency, with low sex steroid concentrations, which was unrelated to the presence of hyperprolactinaemia. In males there was a positive correlation between serum testosterone concentration and GCS (r = 0.32, P = 0.04). One patient had TSH deficiency. Hyperprolactinaemia was present in 26 patients (52%) and serum PRL levels correlated negatively with the GCS score (r =-0.36, P = 0.011). Thirteen patients (26%) had cranial diabetes insipidus (DI) and seven (14%) had syndrome of inappropriate ADH secretion. CONCLUSION: Our data show that post-traumatic neuroendocrine abnormalities occur early and with high frequency, which may have significant implications for recovery and rehabilitation of TBI patients.

Acute Disease↗
PubMed2004

Conventional glucocorticoid replacement overtreats adult hypopituitary patients with partial ACTH deficiency.

BACKGROUND: Glucocorticoid therapy is associated with potentially serious side-effects, but there is no information available regarding glucocorticoid requirement in adult hypopituitary patients with partial ACTH deficiency. SUBJECTS: Ten male adult hypopituitary patients with partial ACTH deficiency, baseline plasma cortisol > 200 nmol/l but a peak stimulated cortisol < 500 nmol/l and 10 matched healthy male control volunteers participated. DESIGN: Patients were assigned, in a random order, to a cross-over protocol of treatment for 1 week with full dose hydrocortisone (10 mg twice daily), half-dose hydrocortisone (5 mg twice daily), or no treatment. All patients completed all three of the treatment limbs. MEASUREMENTS: Following each treatment schedule, patients underwent an 11-h cortisol day curve (CDC), and the results were compared with those from the 10 control volunteers on no glucocorticoid treatment. RESULTS: The integrated CDC values were significantly higher in patients taking a full dose of hydrocortisone compared to controls (P < 0.001). There was no significant difference in the integrated CDC between patients on half-dose (P = 0.37) or no hydrocortisone treatment (P = 0.13), compared to control subjects. Peak postabsorption cortisol values were higher in patients receiving full-dose hydrocortisone treatment compared to controls (P < 0.001). There was no significant difference in plasma sodium concentration, blood pressure or corticosteroid-binding globulin between patients on any treatment schedule and controls. CONCLUSION: Adult patients with pituitary disease and partial ACTH deficiency have a cortisol secretory pattern comparable to that of healthy controls. Conventional full-dose replacement with 10 mg twice daily of hydrocortisone produces hypercortisolaemia, whereas half-dose produces a CDC that is not statistically different from that of healthy controls. The results suggest that current conventional glucocorticoid replacement overtreats patients with partial ACTH deficiency under normal unstressed physiological conditions.

Adrenocorticotropic Hormone↗
PubMed2004

Anterior pituitary dysfunction in survivors of traumatic brain injury.

Recent data suggest that anterior pituitary dysfunction after traumatic brain injury (TBI) is common. We sought to confirm the results of earlier studies in a larger cohort of patients with dynamic testing of pituitary function. We studied 102 consecutive TBI survivors (85 males; median age 28, range 15-65 yr) who had survived severe or moderate TBI (initial Glasgow Coma Scale score 3-13) at a median of 17 months (range 6-36) post event. GH and ACTH reserves were initially assessed using the glucagon stimulation test (GST). Normative data on GH and cortisol responses to the GST were obtained from 31 matched healthy controls. Patients with subnormal GH or cortisol responses were further evaluated, using the insulin tolerance test (ITT) or arginine + GHRH test for GH assessment and the ITT or 250-microg short synacthen test for the assessment of ACTH reserve. Patients were considered to be GH or ACTH deficient if they failed both the GST and the second provocative test. Baseline thyroid function, prolactin, IGF-I, gonadotropins, testosterone, or estradiol was performed in all patients and compared with local reference ranges.In controls, normal response to the GST was a stimulated GH peak of greater than 5 microg/liter and cortisol peak greater than 450 nmol/liter (16 microg/dl). Eighteen TBI patients (17.6%) had GH response to the GST less than 5 microg/liter, 11 of whom also failed the ITT or the arginine + GHRH tests. GH-deficient patients had significantly higher body mass index (P = 0.003), and lower IGF-I concentrations (P < 0.001), than GH-sufficient patients. Twenty-three patients (22.5%) had cortisol responses to GST less than 450 nmol/liter, 13 of whom also failed the ITT or short synacthen test. GH or ACTH deficiencies were not related to age, Glasgow Coma Scale score, or the presence of other pituitary hormone abnormalities (P > 0.05). Twelve patients (11.8%) had gonadotropin and one (1%) had thyrotrophin deficiencies. Twelve patients (11.8%) had hyperprolactinemia. Twenty-nine patients (28.4%) had at least one anterior pituitary hormone deficiency. This is the largest study, to date, of hypopituitarism after TBI and confirms a high prevalence of undiagnosed anterior pituitary hormone abnormalities in survivors of TBI. Hypopituitarism is a treatable cause of morbidity after TBI. In addition to conventional pituitary hormone replacement, the potential of GH treatment to enhance recovery needs to be examined in a prospective study.

Adolescent↗
PubMed2004

Posterior pituitary dysfunction after traumatic brain injury.

Disorders of water balance are well recognized after traumatic brain injury (TBI), but there are no reliable data on their true prevalence in post-TBI patients. We aimed to evaluate the prevalence of posterior pituitary dysfunction in a large cohort of survivors of TBI. One hundred two consecutive patients (85 males) who suffered severe or moderate TBI were evaluated for diabetes insipidus (DI) at a median of 17 months (range 6-36 months) after the event, using the 8-h water deprivation test (WDT). Their results were compared against normative data obtained from 27 matched, healthy controls. Patients' medical records were retrospectively reviewed for the presence of abnormalities of salt and water balance in the immediate post-TBI period. Twenty-two patients (21.6%) developed DI in the immediate post-TBI period (acute DI group), of whom five had abnormal WDT on later testing. In total, seven patients (6.9%) had abnormal WDT (permanent DI group), five of whom had partial DI. Patients in the acute and permanent DI groups were more likely to have more severe TBI, compared with the rest of the cohort (P < 0.05). In the immediate post-TBI period, 13 patients (12.9%) had syndrome of inappropriate secretion of antidiuretic hormone, which persisted in one patient, and one other patient developed cerebral salt wasting. Diabetes insipidus and syndrome of inappropriate secretion of antidiuretic hormone were common in the immediate post-TBI period. Permanent DI was present in 6.9% of patients who survived severe or moderate TBI, which is higher than traditionally thought. Identification of patients with partial posttraumatic DI is important because appropriate treatment may reduce morbidity and optimize the potential for recovery.

Acute Disease↗