Goiter and impairment of thyroid function in acromegalic patients: basal evaluation and follow-up.

AIMS: We evaluated morphological, biochemical and cytological thyroid parameters in acromegalic patients, investigated before and after treatment for acromegaly. PATIENTS: 28 acromegalics were investigated before and, in 18 cases, after 2-7 years of therapy. Fourteen patients were from areas of moderate iodine deficiency in Southern Italy. One patient underwent thyroidectomy before entering this study. RESULTS: 19 patients were euthyroid (FT4: 17.7 +/- 0.8 pmol/l and FT3 4.6 +/- 0.2 pmol/l), but TSH was undetectable in 5/19. Among them, TRH-stimulated TSH increase was absent/impaired or exaggerated/delayed in 9 and one cases, respectively. Decreased FT3 and/or FT4 values with low/normal TSH values were detected in 7 cases; TRH-stimulated TSH response was absent/impaired in 2 patients and exaggerated/delayed in another two. Increased free T4 and free T3 concentrations with undetectable TSH levels were found in one. Two euthyroid patients had high TPOAb levels. Goiter was diagnosed in 21 cases and nodules were found in 14/21. 99Tc scintiscan showed "cold" areas in 13/14 cases and a "hot" nodule in the hyperthyroid patient. Acromegalics from iodine deficient areas showed a not significant increase of prevalence of goiter (86 vs. 71 %) and of mean thyroid volume (35 +/- 7 vs. 28 +/- 4 ml, NS), compared to others. Thyroid volume (TV) did not correlate with GH, IGF-1 and TSH levels, the area under the curve of insulin-increase during OGTT, the age of patients or the duration of acromegaly. Fine needle aspiration biopsy (FNAB), performed in 11/14 patients with nodular goiter, showed colloid nodules in 8 cases, hyperplastic nodules in 2 and an adenomatous nodule in one. Neurosurgery, radiotherapy or medical treatment for acromegaly induced a significant decrease of mean GH and IGF-1 levels (21.5 +/- 8.5 vs. 12.9 +/- 9.6 ng/ml, p< 0.005 and 747 +/- 94 vs. 503 +/- 88 ng/ml, p < 0.02, respectively), but both GH and IGF-1 values normalized only in 3 cases. No significant variation of mean TSH levels was found. Although TV normalized in 3 patients, ultrasound evaluation showed a not significant decrease of mean TV and no changes in the diameter and number of nodules. FNAB was unchanged. CONCLUSIONS: Our results suggest that, despite no correlation between serum GH and IGF-1 levels and thyroid volume being found, a decrease in serum GH and IGF-1 levels has favourable effects on thyroid status.

Short-term effectiveness of low-dose radioiodune ablative treatment of thyroid remnants after thyroidectomy for differentiated thyroid cancer.

Twenty-five patients from a marginally iodine-deficient area with differentiated thyroid cancer who were referred to our unit between 1991 and 1997 had a residual thyroid uptake (RTU) at 24 hours of 5% or more after surgery. None of them underwent reoperation: 8 of 25 had RTU between 5% and 10% and were considered at low risk for both local recurrences and/or distant metastases; 17 of 25 had RTU greater than 10% and up to 30% and refused re-intervention. After detection of their cervical uptake by using a 131I tracer dose of 3.7 MBq (100 microCi), all 25 were treated with 1110 MBq (30 mCi) of 131I. A whole-body scan (WBS) performed 5 days later revealed 131I uptake corresponding to metastatic lymph nodes in the anterior part of the neck in 1 patient and the persistence of only RTU in 24 of 25 patients. RTU and thyroglobulin (Tg) levels were reevaluated 6 months later in all patients and compared to preradioiodine treatment values. RTU, ranging at presentation between 5% and 30%, decreased to below 1% in all but one patient. Serum Tg values, ranging between 1.6 and 108 ng/mL before radioiodine treatment, decreased to below 1.6 ng/mL in all but 4 of them (whose serum Tg was between 2 and 3.4 ng/mL). Our data indicate that 1,110 MBq of 131I can permit complete ablation of 80% of thyroid remnants concentrating up to 30% of radioiodine activity. A relation between this high success rate and iodine deficiency can be hypothesized because an increasing uptake of radioiodine by thyroid remnants could result in overestimation of their size. Therefore, our observations suggest that in iodine deficient areas, a hasty decision to carry out complete thyroidectomy should be avoided, even in the case of thyroid remnants with RTU up to 30%.

Increased risk of maternal thyroid failure with pregnancy progression in an iodine deficient area with major iodine deficiency disorders.

In an effort to assess the impact of moderate iodine deficiency on maternal thyroid function during pregnancy, we measured serum thyrotropin, total and free thyroid hormones, thyroid-binding globulin (TGB) at 8, 14, 20, 29, and 36 weeks of gestation, along with urinary iodide excretion, in 10 healthy women from a moderately iodine deficient region (group A), and compared them with 6 women from an iodine sufficient region (group B). Serum total thyroxine (T4) fell significantly in group A, and was significantly lower than in group B at 29 and 36 weeks (p<0.05). TBG saturation was significantly lower in group A throughout pregnancy, and declined in both groups as pregnancy progressed. Free thyroxine (T4) and triiodothyronine (T3) concentrations fell in both groups, and FT4 values were significantly lower in group A than group B in the third trimester (p<0.05). Urinary iodine excretion was lower in group A women with respect to group B and did not vary significantly in either group as gestation progressed. The serum T3/T4 molar ratio increased through pregnancy only in group B. Thyrotropin concentrations rose in both groups through pregnancy, and were higher in group A at term (p< 0.01). The incidence of isolated hypothyroxinemia or biochemical hypothyroidism doubled (30% to 70%) between midgestation and term in group A, suggesting that moderate iodine deficiency may result in maternal thyroid failure during the later stages of pregnancy.

Thyroid follicular oncogenesis in iodine-deficient and iodine-sufficient areas: search for alterations of the ras, met and bFGF oncogenes and of the Rb anti-oncogene.

To gain insights into the role of iodine deficiency in favoring thyroid tumorigenesis (particularly of the follicular histotype), 22 Sicilian patients with thyroid tumors were selected for having lived permanently in either one of two areas of different iodine availability. Eleven patients (age 46.1 +/- 14.6 years, mean +/- SD; 10 females and 1 male) were from the iodine-deficient (ID) areas of the provinces of Messina and Catania (mean urinary excretion of iodine = 48.1 micrograms/24 hours). Thyroid tumors were follicular or Hürthle cell adenomas (no. = 3), follicular carcinomas (FC, no. = 4), papillary carcinomas (PC, no. = 2) and anaplastic carcinomas (no. = 2). Eleven patients (age 47.1 +/- 15.2 years; 10 females and 1 male) were from the metropolitan area of Messina, an area of relative iodine-sufficiency (IS) (urinary excretion of iodine = 95.2 micrograms/24 hours). These 11 patients had serum levels of TSH that were significantly lower than the corresponding values of the 11 patients from the ID area (0.76 +/- 0.33 vs 1.80 +/- 1.22 mU/l, p = 0.01) The tumors of the 11 patients from the IS area were: follicular or Hürthle cell adenomas (no. = 6), Hürthle cell carcinoma (no. = 1), FC (no. = 2), PC (no. = 2). Molecular biology studies revealed that both the normal as well as the tumor tissue of all 22 patients did not harbor any of the three classical activating mutations (codons 12, 13 and 61) in any of the three ras oncogenes. Similar negative results were obtained as far as loss of heterozygosity of the retinoblastoma (Rb) anti-oncogene is concerned. Immunohistochemistry studies were performed to investigate expression of c-met and basic fibroblast growth factor (bFGF) proto-oncogenes. Only one Hürthle cell carcinoma and the two PC from the IS group, and one FC and the two PC from the ID group stained for the c-met oncogene. Expression of c-met was greater (3+) in the four PC (concerning 70-80% of the tumor cells) than in the other two cancers (1+; < 5% of the tumor cells). In the IS group, positivity for bFGF was detected in 3/6 adenomas, 1/2 FC, the Hürthle cell carcinoma and the two PC. In the ID group, positivity for bFGF was observed in 2/3 adenomas, 2/4 FC, the two PC and the two anaplastic carcinomas. The 8 positive cases from the ID group had a greater level of bFGF expression than the 7 positive cases from the IS group (intensity of staining = 2.0+ vs 1.57+). Interestingly, the greatest expression of bFGF was seen in the cases with peri-tumoral lymphocytic infiltration from either group. In the ID group correlations between (i.) pre-intervention serum TSH and intensity of tumoral staining for bFGF, (ii.) serum TSH and per cent of tumoral cells reactive with anti-bFGF and (iii.) between intensity of staining for bFGF and per cent of tumoral cells bFGF +ve were higher than in the IS group. We conclude that activating mutations of ras, loss of DNA from the Rb locus and over-expression of both c-met and bFGF are of no pathogenetic relevance in driving thyroid tumorigenesis of iodine-deficient areas.

Maternal hypothyroxinaemia during the first half of gestation in an iodine deficient area with endemic cretinism and related disorders.

OBJECTIVE: Iodine deficiency is well known as the cause of several disorders such as endemic goitre and cretinism, along with a wide spectrum of psychoneurological development disorders including endemic mental deficiency and endemic cognitive deficiency, which are generally correlated to damage to the fetus. Such damage is, by inference, deemed a consequence either directly of iodine deficiency or of insufficient availability of thyroxine at the feto-placental unit level. Early pregnancy represents the crucial period for neurogenesis in the embryo. Several experimental studies have emphasized the direct role of maternal T4 in neurological embryogenesis, before the onset of fetal thyroid function and, therefore, its protective role in fetal thyroid failure. The objective of this study was to evaluate whether iodine deficiency may influence thyroid status of pregnant women throughout the first half of pregnancy. DESIGN: Thyroid function tests including total and free T4 and T3, TBG and TSH along with urinary iodine excretion were measured in the serum of pregnant women from an iodine deficient endemic goitre area in north-eastern Sicily, at 8, 13 and 20 weeks of gestation. The times of sampling were chosen to correspond approximately to a period prior to, coincident with and after the onset of fetal thyroid function, respectively. SUBJECTS: The longitudinal study was undertaken in 16 euthyroid pregnant women from the iodine deficient area in which major iodine deficiency disorders such as endemic cretinism and endemic cognitive deficiency in schoolchildren still persist (area A) and in 7 age matched volunteer pregnant women from a marginally iodine sufficient area (area B). MEASUREMENTS: Hormones and TBG were measured using commercial kits. Urinary iodine was measured by an automated method. RESULTS: The divergent changes in serum T4 and TBG with pregnancy progression induced a progressive TBG desaturation by T4 during the whole study period (from 22 to 17% in area A, ANOVA two-way F = 18.9, P < 0.0001; from 33 to 20% in area B, F = 20.7, P < 0.0005) in both areas. At 20 weeks, average FT4 levels were lower in area A than in area B (11.5 +/- 2.5 vs 14.3 +/- 2.4 pmol/l, t = 2.7 P < 0.01) and were below the normal range in 2/16 and borderline-low in 6/16 pregnant women. FT4 serum levels were inversely related to TSH concentrations (r = -0.54, P < 0.0001) which progressively increased, in area A, during the whole study period (F = 6.0, P < 0.01) and were abnormally high in the two women with low FT4, but not in area B. Also in area A (F = 3.4, P < 0.05) a significant T3/T4 molar ratio increase was observed. CONCLUSIONS: Iodine deficiency induces in early pregnancy a series of events (reduced synthesis of maternal T4, TBG desaturation by T4, critical decrease of FT4 levels with consequent TSH increase) responsible for overt or marginal biochemical hypothyroidism in about 50% of pregnant women. It is hypothesized that the imbalance of maternal thyroid hormone homeostasis during pregnancy as a consequence of endemic iodine deficiency may be responsible for the impaired psychoneurological development observed in children from that area so appropriate iodine and/or thyroxine prophylaxis to women in that region may prevent the neurobehavioural, cognitive and motor compromise of the population.

Thyroiditis due to Brucella melitensis.

A case of thyroiditis due to Brucella Melitensis is reported. Brucellosis anticipated by about two months the onset of the characteristic symptoms of acute thyroiditis. Cultures of specimens obtained by fine needle aspiration biopsy and microbiological investigations allowed isolation and identification of the germ. This observation allowed the recognition that thyroid gland might harbored secondary localization of a prolonged brucellosis. A microbiological study (the protocol of which is proposed) of specimen obtained by fine needle aspiration biopsy should be performed in the presence of symptoms and signs of an inflammatory process associated to an acute swelling of the thyroid gland.

Enhanced iodine concentrating capacity by the mammary gland in iodine deficient lactating women of an endemic goiter region in Sicily.

Iodine balance during pregnancy and lactation was investigated by measuring iodine concentration in the urine of 11 pregnant women, born and living in a moderately iodine deficient endemic goiter area in Northeastern Sicily, collected during the last week of pregnancy, and between the 5th and 7th day after delivery, and in their milk sampled simultaneously with the urine of their newborns. The results were compared with those obtained on similar samples from 16 euthyroid age-matched nongoitrous women and their offspring from an iodine sufficient area. Urinary iodine concentration in pregnant women from the endemic area (1.28 +/- 0.13 micrograms/dl, mean +/- SE) was significantly lower than that of pregnant women from the iodine sufficient area (3.77 +/- 0.57 micrograms/dl) (t = 3.56, p less than 0.005). The longitudinal measurement of iodine concentration in each nursing woman showed a marked increase (approximately 90%) when compared with the values obtained during pregnancy in both endemic and control groups (2.32 +/- 0.36 and 7.76 +/- 2.08 micrograms/dl; t = 2.13 p less than 0.05, respectively). The slight difference in milk iodine concentration between the endemic (3.25 +/- 0.77 micrograms/dl) and the control (4.33 +/- 0.57 micrograms/dl) group was not statistically significant (t = 1.14; p less than 0.5, NS). Similarly no difference was found in urinary iodine excretion between the endemic and the control newborn groups (3.41 +/- 0.76 and 4.30 +/- 0.65 micrograms/dl, respectively, t = 0.88 p less than 0.1, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiology and clinical characteristics of endemic cretinism in Sicily.

In this study we report the prevalence of endemic cretinism in the general population of two iodine deficient areas in Northeastern Sicily that were described more than 10 yr ago. In addition, the individual characteristics of endemic cretins are considered in order to define the typical expressions of this major iodine deficiency disorder in Sicily. Forty-three mental defectives were identified: 22 were living in an area with three bordering and closely connected municipalities within the province of Messina and with a population of 17,485 inhabitants (prevalence = 0.13%). Three out of the 22 were school-age children. The other community, in the province of Catania, was constituted by a unique and mostly agricultural hamlet, and showed a prevalence of cretinism that was 0.68% (21/3,100). Among the 43 mental defectives, 16 (37%) presented prominent neuromotor and neurosensorial disorders, including deafmutism and were euthyroid, thus conforming to the neurological type of cretinism; 13 (30%) were hypothyroid and exhibited stunted growth without significant neuromotor and neurosensorial impairment (myxedematous cretins). In the remaining 14 individuals (33%) neurological disorders were associated with stunted growth and clinical or biochemical hypothyroidism. These data indicate that also in Sicily endemic cretinism is a continuum of a variety of forms: among these the pure neurological and pure myxedematous forms represent the two extremes. Our observations also indicate that endemic cretinism still represents a major public health problem in Sicily. The finding of 3 endemic cretins younger than 13 yr suggests the persistence of this disorder even in the presence of improved economic, social and nutritional conditions.

Defective neuromotor and cognitive ability in iodine-deficient schoolchildren of an endemic goiter region in Sicily.

Visual perceptual integrative motor ability was investigated in 719 6- to 12-yr-old, presumably normal, primary schoolchildren living in 2 iodine-deficient endemic goiter areas in Sicily, identified on the basis of the presence (area A) or absence (area B) of endemic cretinism, by administrating the Bender Gestalt test. All of these clinically euthyroid schoolchildren were also examined neurologically by an investigator unaware of the result of the Bender test. Ninety-nine (13.76%) schoolchildren were found to be defective by the Bender test; this prevalence was significantly higher than that (3.0%) found in an iodine-sufficient goiter-free control area (area C) lying at sea level (chi 2 = 36.25; P less than 0.000001). No difference in the prevalence of Bender abnormalities was apparent if the children were divided according to the area of provenience (area A, 14.4%; area B, 13.1%). A high percentage of children falling in the lower range of normality was found in both area A (15.5%) and area B (19.0%); this was significantly higher than that in area C (3.8%; chi 2 = 77.55; P less than 0.000001). Neuromuscular and neurosensorial abnormalities, including increased tendon reflexes, clonus of the foot, Babinski sign, minor disturbances in balance, and gait, and minor defects in hearing and speech, were apparent in 19.3% (area A) and 18.5% (area B) of the children. These disorders were significantly more frequent in defective children identified by the Bender test (33.3%) than in normal children (15.3%; (chi 2 = 17.29; P less than 0.00005). The general intellectual aptitude in Bender deficient subjects was evaluated by the Terman Merrill test and was found to be impaired in 95%, thus confirming the existence of an endemic cognitive deficiency (ECD), distinct from the endemic mental deficiency previously found in other endemic goiter, iodine-deficient areas. ECD seems to be epidemiologically independent of the existence of endemic cretinism. Further clinical auxological and biochemical studies in a selected group of ECD children suggested the epidemiological and, possibly, pathogenic association of cognitive impairment with iodine deficiency.

Partial beneficial effects of the so called "silent iodine prophylaxis" on iodine deficiency disorders (IDD) in northeastern Sicily endemia.

The prevalence of goiter among schoolchildren and the daily urinary iodine excretion in the general population were evaluated in 4 municipalities in the endemic goiter area in Northeastern Sicily in two different surveys. The first, carried out in 1977-1978, covered 2,493 (91%) schoolchildren; the second, in 1987-1988, covered 2,167 (92%) schoolchildren. A dramatic decrease in goiter prevalence was apparent in each community as follows: in Castell'Umberto (3,904 inhabitants, altitude 641/750 m above sea level) goiter prevalence (G) decreased from 79.7% to 44.2% with a percent reduction (%r) of 44.5 and an increase in 24-h urinary iodine excretion (UIE) from 22.3 +/- 16.4 micrograms/24 h (n = 30) to 48.7 +/- 43.4 (n = 50). A similar trend was apparent in Tortorici (10,194 inhabitants, 475/700 m) where G decreased from 62.2 to 26.5% (% r 57.4) with a UIE increase from 28.4 +/- 29.6 (n = 35) to 47.6 +/- 59.3 (n = 40); in Sinagra (3,387 inhabitants, 300 m) where G decreased from 61.6 to 32.7% (% r 46.9) and UIE increased from 26.0 +/- 21.1 (n = 25) to 66.6 +/- 69.6 (n = 102) and in Sant'Angelo di Brolo (5,732 inhabitants, 380 m) where G decreased from 48.7 to 27.5% (% r 43.5) and UIE increased from 26.3 +/- 16.7 (n = 30) to 47.7 +/- 73.8 (n = 34). These events are clearly related and certainly dependent on the changed alimentary habits in the area due to the improved distribution of frozen food and industrially prepared dairy products, eventually enriched by iodine.(ABSTRACT TRUNCATED AT 250 WORDS)