Also, we demonstrated that TRH Receptor 1 (TRH-R1) is colocalized in NEI immunoreactive neurons in the peduncular part of the lateral hypothalamus (PLH) and NEI precursor mRNA expression increased by hypothyroidism indicating that NEI neurons are responsive to the feedback mechanisms of the Hypothalamic Pituitary-Thyroid Axis (HPT).
Due to case reports of thyroid dysfunction in 18q deletions and the well-established association between hypothyroidism and aneusomies, we undertook thyroid testing in all individuals and completed TRH studies on 50 of them.
The syndrome is characterized by: adipsia-hypodipsia (5/5 patients), recurrent hypernatremia (5/5), obesity (4/5), inability to excrete a water load (5/5), lack of growth hormone release in response to provocative stimuli (4/4), blunted thyrotropin releasing hormone responses (3/4), hypothyroidism (2/4), and hyperlipemia associated with hypernatremic crisis (1/1).
In addition, the absence of hypothyroidism and normal responsiveness of serum TSH to TRH and L-triiodothyronine administration in untreated family members suggest that the thyroid has compensated for the hormone resistance by increased secretory activity under the control of pituitary TSH secretion.
It is suggested that 1) among euthyroid relatives with a family history of Graves' disease, there are many with abnormalities in TRH responsiveness and T3 suppressibility, 2) nonsuppressible subjects are more likely to be TRH hyporesponders and vice versa, 3) hyperthyroidism or hypothyroidism occurs frequently in euthyroid relatives with a family history of Graves' disease, and 4) thyrotoxicosis occurs frequently in TRH-hyporesponders, and hypothyroidism occurs in the others.
However, an abnormally exaggerated TSH response to TRH was observed not only in the hypothyroid patients but also in six of the other subjects, indicating a decreased thyroid feedback at the pituitary level in the presence of a normal serum concentration of thyroid hormones.