Postintervention serum TSH levels may be useful to differentiate patients who should undergo levothyroxine suppressive therapy after thyroid surgery for multinodular goiter in a region with moderate iodine deficiency.

Recent studies have raised doubts about the efficacy of the postoperative use of levothyroxine (LT4) suppressive doses in patients who underwent thyroid surgery for multinodular goiter. The purpose of this retrospective study was to examine the efficacy of different doses of LT4 in preventing postsurgical recurrences of simple multinodular goiter and to identify a marker that could be useful in discriminating patients with a higher risk of developing recurrence. Two hundred thirty-two patients (57 male, 175 female) operated for nontoxic multinodular goiter were divided into two groups: (I) patients with normal postsurgery thyrotropin (TSH) levels (0.25 to 4.5 mU/L) and (II) patients with elevated postsurgery TSH levels (>4.5 mU/L). All patients were subjected to replacement (1.3 microg LT4/kg/day) or suppressive (1.7 microg LT4/kg/day) doses of LT4, and they were followed for a median period of 6 years (range 2 to 12). No statistical difference was found for sex, age, and postsurgery serum TSH between patients submitted to suppressive and replacement therapy. The ultrasound (US) detection of new postsurgery nodules of at least 0.5 cm maximum diameter was considered a recurrence of disease and was found in 10% of the cases studied. Patients with normal postsurgery serum TSH showed a high recurrence rate (30.4%) when submitted to lower daily doses of LT4. In patients with elevated postsurgery serum TSH, the rate of nodular goiter recurrence did not vary with different types of LT4 therapy. In conclusion, our results suggest that the postsurgical serum TSH is useful for prediction of nodular goiter recurrence, as it reflects the amount of residual functioning thyroid tissue in the cervical area. It may also be indicative of patients who might benefit from LT4 suppressive therapy.

Diabetes insipidus and increased serum levels of leptin and lactate-dehydrogenase (LDH) in an adolescent boy with a primary intracranial germinoma. Case report and an endocrinological revaluation of literature.

A 16-year-old boy presented with a four-month history of polyuria-polydipsia and a diplopia which had reverted after treatment. The neuroimaging studies performed had been strongly suggestive of an optic nerve glioma, while endocrinological investigation (beta-hCG 420 IU/L) has lead to the correct diagnosis later confirmed at the immunohystochemical analysis performed at biopsy. The high serum level of hCG was unaffected by bromocriptine nor octreotide, while the PRL level (80.0 microg/L) was reduced only by bromocriptine. Among the several tumor markers which may be secreted by such lesions, ours is the first reported case of an elevation of serum LDH for a primary intracranial germinoma. Moreover, the elevated value of serum leptin reported by us might be due to the insensitivity of the hypothalamic structures to endogenous leptin.

An improved polymerase chain reaction (PCR) protocol for unambigous detection of growth hormone gene deletions.

hGH-1 gene deletions are detected by simultaneous PCR amplification along the two homologous DNA sequences flanking the hGH-1 gene on both sides and are differentiated by SmaI restriction enzyme digestion. We have observed that among the SmaI digested PCR products from normal homozygous subjects, from those heterozygous for the 7.6 kb deletion and from those heterozygous for a 6.7 kb deletion, along with the expected fragments there is an unexpected 1470 bp fragment. This fragment arises from the co-amplification of a third homologous sequence located downstream from the hGH-1 gene and it confuses differentiation between normal homozygous and heterozygous for 7.6 kb subjects from the 6.7 kb heterozygous subjects. To overcome this problem we have improved PCR conditions using a different reverse primer. These changes avoid the interaction of the primers with the third homologous sequence located downstream from the hGH-1 gene and prevent the appearance of this additional band that complicates the interpretation of the results. We conclude that the new reverse primer sequence avoids the amplification of the downstream hGH-1 gene sequence and the production of the 1474 bp band after SmaI endonuclease enzyme digestion and makes it possible to differentiate homozygous normal subjects and those who are heterozygous for a 7.6 kb deletion from those who are heterozygous for a 6.7 kb deletion.

Occurrence of thyroid autoimmunity and dysfunction throughout a nine-month follow-up in patients undergoing interferon-beta therapy for multiple sclerosis.

Thyroid autoimmunity and dysfunction are a well known side effect of IFN alpha therapy for viral hepatitis and tumors, while the IFN beta effects on the thyroid gland in neurological patients have not been studied. The aim of this longitudinal study was to look for the appearance of thyroid autoimmunity as well as for the occurrence of overt thyroid disease in the patients affected by multiple sclerosis (MS) treated with IFN beta 1b. Eight patients (4 males, 4 females) undergoing r-IFN beta 1b treatment (8 M.U. every other day for 9 months) for relapsing remitting multiple sclerosis entered the study. We have analyzed thyroid function parameters and auto antibody levels before and after 1, 2, 3, 6 and 9 months of therapy. None of them referred to familiar thyroid pathology or presented clinically overt thyroid disease except for one patient (case 4) who showed TPO-Ab pretreatment positivity and another (case 8) who was in therapy with Levothyroxine 100 microg/die for multinodular goiter. The number of patients with appearance of thyroid antibodies has slowly increased, until the third month of therapy with 3 patients out of 7 positive for TPO-Ab. The only case of overt thyroid dysfunction reported by us appeared after nine months of therapy and consisted of a hypothyroidism. Our data suggest that short-term interferon beta treatment is able to induce thyroid autoimmunity (42.8%) and dysfunction (12.5%).

Melatonin and the pituitary-thyroid axis status in blind adults: a possible resetting after puberty.

OBJECTIVE: Increased levels of free thyroid hormones have been previously described in prepubertal blind subjects and have been thought to be a consequence of a partial target organ refractoriness due to the early and prolonged lack of light perception. The aim of this study was to clarify whether this abnormality is permanent or transient and the interrelationships between melatonin and thyroid hormone secretion. MEASUREMENTS: Total and free thyroid hormones, TSH, thyroxine-binding globulin (TBG), reverse triiodothyronine (rT3) and melatonin were measured in plasma samples obtained at 0800 h (two hours after lights-on) in a group of 11 totally (group 1) and 16 partially (group 2) blind adult patients and in 10 age-matched healthy subjects. RESULTS: Both totally and partially blind patients showed melatonin levels higher than in controls (330 +/- 106 pmol/l, group 1 and 361 +/- 159 pmol/l, group 2, respectively; controls: 53 +/- 12 pmol/l, P < 0.001 vs both groups), but fT4, fT3, T4, T3 TSH, rT3 and TBG concentrations showed no significant differences from controls. CONCLUSIONS: A possible resetting of pituitary-thyroid axis regulation can occur in blindness after puberty; variations of melatonin secretion could play a role in this. The inhibitory effect of melatonin on thyroid gland function found in animals does not seem to occur in humans. Elevated melatonin levels, both in patients with total blindness and in those with light perception only, suggest that more complex mechanisms other than light signalling are involved in the changes of melatonin secretion in blindness.

Normal plasma insulin-like growth factor I levels and impaired final stature in adult blind subjects.

The aim of this study was to determine if changes in IGF-1 levels and in final stature occur in blind adult subjects. Eighteen subjects (4 females and 14 males) with total blindness (Group 1) and 26 subjects (5 females and 21 males) with only light perception (Group 2), living at an Institute for blind adult subjects in Naples, Italy, were studied. Their height and weight were compared to British standards. Plasma morning IGF-1 levels, measured by IRMA method were compared to those of 18 normal controls (6 females and 12 males) matched for age and weight. A high prevalence of short stature was demonstrated especially in Group 1 (p = 0.00005 by chi-square for trend test) but was also present in Group 2 (p = 0.02). No alterations in weight distribution were observed in both groups. Basal IGF-I levels in both Group 1 and Group 2 were similar to those of controls: IGF-1 (M +/- SE), 30.9 +/- 2.9 nmol/L and 37.9 +/- 2.7 nmol/L, respectively, vs 33.3 +/- 2.9 nmol/L, NS. High prevalence of final short stature in both groups confirms a negative influence of total or partial blindness on growth. These complex mechanisms appear to involve more than alterations in GH and IGF-I secretion.

Circannual variations of plasma testosterone, luteinizing hormone, follicle-stimulating hormone and prolactin in Klinefelter's syndrome.

To clarify the influence of primary testicular failure upon circannual hormone rhythmicity we have been studying, by cross-sectional design, 93 adult patients with Klinefelter's syndrome (KS) and 64 adult healthy males to look for evidence of circannual rhythms in testosterone (T), LH, FSH and PRL plasma concentrations. Plasma samples were taken from 08.00 to 09.00 h and all hormones were measured by radioimmunoassay. The data were assessed by the single cosinor method in order to obtain evidence for any significant rhythm and to estimate its parameters mesor, amplitude and acrophase. In the controls, annual rhythms were validated for the secretion of T (annual crest time in September), LH (annual crest time in February) and FSH (annual crest time in January), whereas PRL did not show a significant annual rhythm. In KS, significant circannual rhythms were validated for the secretion of T (annual crest time in April) and FSH (annual crest time in September), but not for LH and PRL secretion. Our results suggest that in KS the circannual hormone rhythmicity may be influenced by seminiferous tubule dysgenesis.

Persistent TRH-induced growth hormone release after short-term and long-term L-thyroxine replacement therapy in primary congenital hypothyroidism.

No appreciable changes in plasma GH levels after TRH stimulation have been observed in normal subjects, whereas acute GH release has been reported in primary hypothyroidism and other pathophysiological states. To evaluate the effect of the T4 replacement therapy on TRH-induced GH release, 28 patient volunteers with primary congenital hypothyroidism (PCH), were studied before (11 subjects), after 1 month (nine subjects) and after long-term T4 replacement therapy (eight subjects). All patients underwent a TRH test with measurement of TSH, PRL and GH levels, and were compared to 28 age-matched normal subjects. An increase of plasma GH after TRH was found in 46% of patients without any therapy, in 67% of patients after one month of T4 administration and in 75% of patients after long-term therapy. No changes were observed in plasma GH levels in controls. The TSH response to TRH was inhibited and the response of PRL was reduced step by step by T4 replacement therapy in our patients with PCH. Our results suggest that: (i) Replacement T4 therapy in PCH does not abolish the paradoxical GH response to TRH, in spite of inhibiting the TSH response and reducing the exaggerated PRL response; (ii) the GH response to TRH in PCH seems to be unrelated to low thyroid hormone levels and/or to high TSH levels, but it could be due to changes in hypothalamic-pituitary regulation which are not improved by T4 replacement therapy.

Change in circadian cortisol rhythmicity in patients with intracranial tumour.

To verify the influence of intracranial expanding processes on circadian cortisol rhythm, we studied its occurrence in 10 normal subjects, in 5 patients with extrasellar tumour, and in 3 patients with intracranial haematoma. All patients were tested every 4 h. Cortisol was measured by RIA. A cosine function was fitted to the data by mean cosinor method to evidence any rhythm and its parameters. A significant circadian rhythm was detected in the normal subjects with acrophase at 07.55 (07.15-08.25). The patients with extrasellar tumour and those with intracranial haematoma showed a lack of circadian rhythmicity due to a significant increase of cortisol levels at 20.00 and at 00.00, respectively. Our results suggest that study of the cortisol rhythm is useful, especially when an extrasellar tumour is suspected.