The role of radioactive iodine usage in the management of thyroid disorders with emphasis on sub-Saharan Africa.

BACKGROUND: Radioactive iodine (RAI) usage is increasingly becoming a standard therapeutic and diagnostic measure in the management of thyroid disorders. Despite these advances, there are varying opinions on the appropriate usage of this treatment option of thyroid disorders. In sub-saharan Africa, reports on RAI in the management of thyroid disorders are scanty and RAI usage is shrouded in mystery. OBJECTIVES: This review article sought to evaluate the role of RAI in the diagnosis and treatment of thyroid disorders with emphasis on its usage in Africa. It also addresses specific areas of concern amongst others such as RAI use in children, in large compressive goiters, reproductive function and the issue of associated iatrogenic hypothyroidism. METHODS: A systematic review of literature--local and otherwise--on radioactive iodine usage from indexed and online journals using Pubmed, Google and Google Scholar in the period between 1942 till 2007. RESULTS: The most common complication of RAI therapy is hypothyroidism which appears to be almost inevitable. There is controversy as to whether RAI therapy is a risk factor for thyroid cancer or cancer of other iodine-concentrating organs. Equally controversial is whether RAI leads to infertility or genetic disorders of children whose parents were treated with RAI. The use of RAI in the diagnosis and treatment of thyroid disorders appears unduly limited. CONCLUSION: Radioactive iodine--a major tool in the diagnosis and management of benign and malignant thyroid disorders--is underutilized in the African. There is a need for heightened awareness amongst endocrinologists from the African continent on the usage of this all-important treatment modality of thyroid disorders.

A follow up report: recurrent Cushing's syndrome after bilateral adrenalectomy.

This is a case report of a 23 year old female. She had earlier been diagnosed to have Cushing's syndrome due to macronodular adrenal hyperplasia, for which bilateral adrenalectomy was performed three years before. The initial full recovery was sustained for about one and a half years, following which there was progressive recurrence of obesity, hypertension and hypercalcaemia. Plasma cortisol concentrations were markedly elevated and a diagnosis of recurrent Cushing's syndrome was made. Pre-operative localisation of the source of hypercortisolism through intravenous urogram, abdominal ultrasonogram and computerised tomogram was unfruitful, thus an exploratory laparatomy was undertaken. At surgery, extensive and dense adhesions were seen which caused difficult dissection and accidental injury to the patient's liver and kidney, necessitating massive intra-operative blood transfusions. The patient died within two hours of recovery from anaesthesia of acute massive pulmonary embolism. We postulate that the recurrent Cushing's syndrome in this patient could have been due autografting of remnants of adrenal tissue within the abdominal cavity. A pre-operative localisation with radio-labelled cholesterol scanning may have made reoperation of the patient easier.

Congenital adrenal hyperplasia due to 11-hydroxylase enzyme deficiency in three siblings. A brief report.

To appraise clinicians of the presence of an uncommon cause of congenital adrenal hyperplasia in a Nigerian family, we present case reports of three siblings comprising two males (aged 4 years 10 months and 3 years 10 months) and a female (aged 16 months). The male patients presented with features of precocious pseudopuberty and had body weights and heights that were above the 95th percentiles on a standard growth chart. There was radiologic evidence for an advanced bone age of over 11 years in both patients, together with findings of sustained systemic hypertension. The female patient was discovered to have an abnormal hormonal profile during a screening of the unaffected children of their non-cosanguinous monogamous parents. The three siblings had morning plasma cortisol concentrations in the lower range of reference values together with markedly elevated levels of plasma androgens. These biochemical abnormalities together with the clinical features of precocious pseudopuberty in the two male patients led to the clinical suspicion of congenital adrenal hyperplasia (CAH). The enzymatic defect was believed to be due to 11-hydroxylase enzyme, because of the presence of sustained systemic hypertension in the male subjects. As routine family screening was instrumental in the discovery of the subclinical CAH in the female subject, it is thus suggested that clinicians should endeavour to undertake a detailed hormonal screening of family members of patients.

Unilateral macronodular adrenal hyperplasia as an unusual cause of Cushing's syndrome--a case study.

To appraise clinicians of the problems that may be encountered in the diagnosis and management of Cushing's syndrome, we present a case report of a 20-year old female, who was admitted with a recently developed central obesity, ammenorrhea hirsuitism, proximal myopathy and depression. She was found to have multiple striae, thin skin, elevated blood pressure glycosuria and hyperglycaemia. Morning and mid-night plasma cortisol concentrations revealed elevated levels, with a loss of diurnal variation. There was a failure of the normal suppressibility of cortisol secretion by low doses of dexamethasone, while a significant suppression of plasma cortisol concentration was observed with high doses of dexamethasone. There were no significant abnormalities observed in the pituitary fossa on skull radiograph and on the cranial computerised tomographic scan. After a period of stabilisation, she had a bilateral adrenalectomy done, with a histopathological finding of a left adrenal macronodular hyperplasia, while the right adrenal gland was small and friable. There was an uneventful post-operative period, with a gradual return to normality of most of the presenting complaints. The hyperglycaemia and hypertension got controlled without medications, while her menstrual cycles resumed within three months of bilateral adrenalectomy. This case report illustrates that an adrenal-dependent Cushing's syndrome may mimic a pituitary-dependent one, especially as regards the suppressibility of plasma cortisol secretion by high doses of dexamethasone.

A study of thyroid function and prevalence of thyroid autoantibodies in an African diabetic population.

It is generally believed that autoimmune disorders are uncommon in Africans. Some workers have argued that insulin-dependent diabetes mellitus (IDDM) is rare in Africa on account of this reduced proneness to autoimmunity. However, it is undetermined whether or not Africans with IDDM have increased prevalence of thyroid dysfunction and autoimmunity, two phenomena strongly associated with Caucasian IDDM. We determined thyroid function and the prevalence of thyroid autoimmunity in IDDM Africans. The results are compared with those of a nondiabetic group and a group with non-insulin-dependent diabetes mellitus (NIDDM). Thyroid hormone levels were significantly lower in IDDM patients than in the control population and the NIDDM population. Subclinical hypothyroidism was present in 21% of the 28 IDDM patients. One patient was hypothyroid and another hyperthyroid. Of the 60 NIDDM patients, 5 (8.3%) had subclinical hypothyroidism. Forty-six percent of the IDDM patients had significant levels of serum thyroid autoantibodies (TAAB). This was significantly higher than the 1.4% and 1.7%, respectively, in the controls and NIDDMs. Presence of TAAB in the patients was strongly associated with thyroid dysfunction, female preponderance, and duration of diabetes mellitus. Thyroid dysfunction and autoimmunity are common in Nigerians clinically diagnosed as IDDM, and have prevalence rates comparable to other populations but higher than rates previously reported from some other African groups. The increased prevalence of thyroid autoimmunity in the IDDM supports the view that these patients are true IDDMs rather than variants of NIDDM or malnutrition-related diabetes mellitus (MRDM) as has been suggested by some workers.

Cardiac involvement (Wolff-Parkinson-White syndrome) in tuberous sclerosis.

A surface electrocardiogram showing type B Wolff-Parkinson-White syndrome pattern was part of the cardiac findings in a female of 24 with florid features of tuberous sclerosis. She had cardiomegaly but no intracardiac tumour was demonstrated. Wolff-Parkinson-White syndrome, though rare, has previously been described in association with tuberous sclerosis in children but not before in adults.

Oligo/azoospermia in Nigeria.

Oligo/azoospermia contributes significantly to infertility in male Nigerians, being responsible for most of the problem. By definition, it would appear that the criteria for the diagnosis of this problem in Nigerians should be sperm density below 10 million/ml, total sperm ejaculate below 25 million, motility below 40%, and normal forms below 40% in agreement with more recent findings in other parts of the world. This reinforces the already generally accepted that the WHO may need to review its criteria for diagnosing oligo/azoospermia. Preventable causes of oligo/azoospermia in Nigeria include poorly treated infections such as venereal diseases, delayed treatment of torsion of the testis and of undescended testis, and repair of inguinal hernia by inexperienced native doctor [3, 4]. In addition, better approaches to the diagnosis of causes of infertility, such as a careful search for and rational treatment of varicocele, may improve the chances of infertile couples. Hormonal disorders are important factors to consider in oligo/azoospermic Nigerians, as with their counterparts elsewhere. Wide-spread availability of hormonal assays will therefore be a great help in separating the untreatable (primary testicular disease) from the treatable (hypothalamic/pituitary) diseases and planning rational treatment. With improvement of clinical care, many more patients with sickle-cell disease are reaching reproductive age. Oligo/azoospermia is quite common in patients with sickle-cell disease, and sickle-cell disease will eventually contribute more proportionately to the etiology of oligo/azoospermia in Nigerians. Extensive investigations have been conducted on the nature, etiology, and diagnosis of oligo/azoospermia [2-11, 25, 30-56].(ABSTRACT TRUNCATED AT 250 WORDS)

Serum levels of gonadotropins, prolactin, and testosterone in oligo/azoospermic Nigerian males.

To determine the frequency of hormonal abnormalities in a Nigerian population of male partners of infertile relationships, serum levels of luteinizing hormone, follicle-stimulating hormone, prolactin, and testosterone were estimated using radioimmunoassay techniques in 454 oligo/azoospermic male partners of infertile marriages. Of these men, 272 (59.9%) had an abnormal serum level of one or more of the hormones. Hyperprolactinemia, found in 144 patients, was the most common hormonal disorder in the group. Elevated serum gonadotropins associated with low serum testosterone were found in 120 (26.4%) patients, while 32 (7%) had a reduced serum testosterone concentration in association with low serum gonadotropins. Since hyperprolactinemic, hypogonadotropic, and normogonadotropic testicular failures are amenable to treatment, routine hormonal evaluation of male partners of infertile marriages is suggested in Nigeria and other places where this practice is uncommon at present.

Serum levels of gonadotropins, prolactin, and progesterone in infertile female Africans.

To determine the prevalence of hormonal abnormalities in infertile African women, serum levels of luteinizing hormone, follicle stimulating hormone, prolactin, and progesterone were estimated using radioimmunoassay techniques during the midluteal phase in 2,047 female partners of infertile relationships. Of the patients investigated, 1,085 (53%) had abnormal serum levels of one or more of the hormones studied. Hyperprolactinemia, found in 537 (26.2%) of the patients, was the commonest hormonal abnormality. Serum progesterone level of 3 ng/mL or below which is indicative of anovulation was found in 235 (11.5%) patients, while the value of 5 ng/mL or below, suggestive of inadequate luteal functions, was found in another 121 (5.9%) patients. Since hyperprolactinemia, anovulation, and defective luteal function are treatable endocrine disorders, routine endocrine evaluation of infertile females in African societies is suggested.

Plasma insulin and human growth hormone patterns in an African population.

Low fasting blood sugar levels and insulin sensitivity have been consistently reported in Africans. To study the role played by insulin and growth hormone (HGH) in the genesis of this state, plasma insulin and HGH levels were measured in 40 healthy fasting Africans. Mean plasma insulin and HGH were 10.7 +/- 1.3 muU/ml and less than 1 muU/ml respectively. These are in the same range reported for Caucasians in the literature. The response of plasma insulin and HGH to a menal was further studied in 80 healthy Africans. While insulin response was brisk and adequate, the HGH response was rather sluggish. The significance of these findings is discussed.

Renal handling of homologous radioiodinated thyrotrophin in the rat.

Previously, TSH metabolism and tissue distribution in the rat were studied using heterologous hormone and/or unphysiological doses. We injected iv [131I]rTSH (S.A. 100 micronCi/microgram) in physiological doses (10 ng) to KI blocked male rats. Two to 180 min after which TCA precipitable 131I was measured in the kidney, liver, muscle, fat and testis. The highest TCA precipitable radioactivity concentration, peak value 12% at 30 min; organ/blood ratio, 16, was found in the kidney. With the kidney validated as the major site of localization of TSH, the renal localization and handling of [125I]rTSH was studied by autoradiography. Radioactivity was confined to the cortex. Two to 30 min samples showed 125I in Bowman's space and luminal parts of the proximal tubular cells while samples from 60 to 180 min revealed activity in contraluminal areas, suggesting glomerular filtration and tubular re-absorption. Gel-filtration of supernatants of kidney homogenates revealed progressive diminution of the TSH peak and the appearance of a smaller MW peak. We conclude that (1) the kidney is the major site of localization and metabolism of homologous TSH, (2) the renal handling of TSH involves both glomerular filtration and tubular re-absorption.

A prospective study of glucose tolerance, insulin, C-peptide, and glucagon responses in patients with pancreatic carcinoma.

Ninety-nine patients suspected of having pancreatic carcinoma were studied prospectively for carbohydrate tolerance. Thirty-two patients were proven subsequently to have pancreatic carcinoma; the remainder served as a control group. There was an increased incidence of carbohydrate intolerance in patients with pancreatic carcinoma compared to the control group. Insulin and C-peptide measurements during glucose tolerance tests suggest abnormal beta cell function and possibly insulin resistance as causes for this abnormality. Although factors related to malignancy in general could partly account for the results, a specific factor occurring in patients with pancreatic carcinoma must also be considered as it could serve as a marker for the early detection of this disease.

Plasma glucagon, insulin and glucose responses to intravenous arginine infusion in the rat.

Plasma glucagon (IRG), insulin and glucose responses to intravenous arginine infusion in the rat were studied. Three doses of arginine hydrochloride were infused into fasted rats: 0.2 gm/kg b.w., 0.5 gm/kg b.w., and 1 gm/kg b.w. The 0.2 gm/kg dose did not result in significant elevation of plasma IRG or insulin. Both the 0.5 and 1 gm/kg doses produced a significant increase in glucagon and insulin levels within 5 minutes of starting the infusion. The 1 gm/kg dose was most effective in stimulating secretion of both hormones. This dose produced a 250% rise in the plasma IRG compared to 80% peak rise with the 0.5 gm/kg dose (p less than .01) and 1055% rise in insulin levels compared to a peak level of 225% above baseline with the 0.5 gm/kg dose (p less than .001). These results demonstrate the effectiveness of intravenous arginine in the stimulation of glucagon and insulin secretion in the rat.

Pathogenesis and characterization of hyperglucagonemia in the uremic rat.

The pathogenesis of hyperglucagonemia and of the alterations in the pattern of circulating immunoreactive glucagon (IRG) associated with renal insufficiency was studied in rats in which a comparable degree of uremia was induced by three different methods, i.e., bilateral nephrectomy, bilateral ureteral ligation, and urine autoinfusion. Nephrectomized and ureteral-ligated rats were markedly hyperglucagonemic (575 +/- 95 pg/ml and 492 +/- 54 pg/ml, respectively), while IRG levels of urine autoinfused animals (208 +/- 35 pg/ml) were similar to those of control rats (180 +/- 26 pg/ml), indicating that uremia per se does not account for the hyperglucagonemia observed in renal failure. Similarly, plasma IRG composition in this group of animals was indistinguishable from that of controls, in which 88.2 +/- 5.9% of total IRG consisted of the 3,500-mol wt fraction. The same component was almost entirely responsible (82.6 +/- 4.1%) for the hyperglucagonemia observed in ligated rats, while it accounted for only 57.6 +/- 5.0% of the circulating IRG in nephrectomized animals. In the latter group, 36.8 +/- 6.6% of total IRG had a mol wt of approximately 9,000, consistent with a glucagon precursor. This peak was present in samples obtained as early as 2 h after renal ablation and its concentration continued to increase with time reaching maximal levels at 24 h. These results confirm that the kidney is a major site of glucagon metabolism and provide evidence that the renal handling of the various circulating IRG components may involve different mechanisms. Thus, the metabolism of the 3,500-mol wt fraction is dependent upon glomerular filtration, while the uptake of the 9,000-mol wt material can proceed in its absence, as long as renal tissue remains adequately perfused. This finding suggests that the 9,000-mol wt component may be handled by peritubular uptake.

Heterogeneity of plasma glucagon. Circulating components in normal subjects and patients with chronic renal failure.

Plasma immunoreactive glucagon (IRG) concentrations were measured in 36 patients with chronic renal failure (CRF) and 32 normal subjects. In addition, the components of circulating IRG were analyzed by gel filtration in the fasting state and after physiological stimuli. Fasting IRG was elevated (P less than 0.001) in CRF patients (534 +/- 32 pg/ml) compared with the levels found in healthy subjects (113 +/- 9 pg/ml). Oral glucose suppressed plasma IRG in CRF patients from a basal level of 568 +/- 52 to a nadir of 354 +/- 57 pg/ml (120 min). This degree of suppression (38%) was comparable to that found in normal subjects (basal = 154 +/- 20 to 100 +/- 23 pg/ml) at 120 min (35%). Intravenous infusion of arginine (250 mg/kg) resulted in a 71% rise in IRG in CRF patients and a 166% increase in normal subjects. Gel filtration of fasting plasma from CRF patients showed three major peaks. The earliest (A) was found in the void volume (mol wt greater than 40,000) and constituted 16.5 +/- 4.7% of the elution profile. The middle peak (B) eluted just beyond the proinsulin marker (approximately 9,000 mol wt) and constituted the largest proportion of the elution profile (56.5 +/- 3.4%). The third peak (C) coincided with the standard glucagon and [125I]glucagon markers (3,485 mol wt) and comprised 27.0 +/- 4% of the IRG profile. In contrast, only peaks A and C were found in fasting plasma of normal subjects (53.6 +/- 10.4% in A and 46.4 +/- 10.4 in C). After oral glucose, glucagon immunoreactivity in the 3,500 mol wt peak (C) was markedly suppressed, while the B peak in patients with CRF declined to a lesser extent. The A peak in both groups was unchanged. After an arginine infusion only the C peak increased in both groups of subjects. Gel filtration of plasma in 3 M acetic acid gave similar profiles to those obtained in glycine albumin buffer. Exposure of serum to trypsin indicated that the B and C peaks were digestible, while the A peak was resistant to the action of the enzyme. In one sample, peak C increased after a 2-h exposure of serum to trypsin. We conclude that circulating IRG in normal subjects and patients with CRF is heterogenous. The hyperglucagonemia of renal failure is largely due to an increase in IRG material of approximately 9,000 mol wt, consistent with proglucagon, although the 3,500 mol wt component is also considerably elevated (threefold). The significance of circulating IRG levels should be interpreted with caution until the relative biological activity of the three components is established.

Infusions of hFSH and hLH in normal men. I. Kinetics of human follicle stimulating hormone.

Serial serum assays of immunoreactive FSH before, during and after a 4 h intravenous infusion of human follicle stimulating hormone (hFSH) in five healthy men revealed two disappearance rate constants with corresponding mean half-lives of 2.9 and 50.6 h. The mean distribution spaces calculated for the fast and slow component were 4.36 1 and 75.9 1 respectively. The average value for the metabolic clearance rate was 17.2 ml/min and for the endogenous production rate 50.9 mU/min. Two of the subjects had human luteinizing hormone (hLH) added in the infusions without the FSH kinetics changing.

Infusions of hFSH and hLH in normal men. II. Serum testosterone response to infused hLH and hFSH.

Standardized 4 h intravenous infusions of human follicle stimulating hormone (hFSH) and/or human luteinizing hormone (hLH) were given either separately or combined to 7 normal male volunteers. The infusions raised the serum gonadotrophin levels at least 10 (FSH) and 18 (LH) times above the basal ones. Serum testosterone (T) levels were measured serially before, during and after the infusions and, in 4 subjects, during a corresponding period of another normal day. During a normal or basal 24 h period fluctuations were seen and also a circadian rhythm with lower levels in the evening. The infusion of hFSH alone (3 subjects) did not alter the serum T levels. The infusion of hLH alone in 2 subjects raised serum T levels by 17% and 55% over those of the basal day. The combined FSH/LH infusion caused a significant rise (35-68%) in 4 subjects and greater rise in 2 of them than after infusion of the hLH alone. The serum T responses were gradual, reaching a maximum 7-8 h after the end of the infusion.

Heterogeneity of plasma glucagon: patterns in patients with chronic renal failure and diabetes.

Immunoreactive plasma glucagon (IRG) in normal subjects and patients with chronic renal failure, diabetic ketoacidosis and diagetic hyperosmolar syndrome circulates in several forms. In the diabetic patients most IRG eluted coincidentally with the extracted, purified pancreatic hormone (MW3500), while in normal subjects a high molecular weight component predominated. In striking contrast, the major component of plasma IRG in patients with chronic renal failure was of intermediate size (MW +/- 9000), consistent with proglucagon. The accumulation of this form of IRG suggests that the kidney plays an important role in its metabolism. If there are differences in the biological activity of the various circulating components of IRG, the significance of immunoreactive glucagon levels in some disease states will require reassessment.