Hypothyroidism due to TSH receptor mutations

What it is

From: Orphanet

A type of primary congenital hypothyroidism, a permanent thyroid hormone deficiency that is present from birth due to thyroid resistance to TSH.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Congenital hypothyroidism · Very frequent (99-80%)

A type of hypothyroidism with congenital onset.

Elevated circulating thyroid-stimulating hormone concentration · Very frequent (99-80%)

Increased concentration of thyroid-stimulating hormone (TSH) in the blood circulation.

Impaired sensitivity to thyroid stimulating hormone · Obligate (100%)

Reduced sensitivity of thyroid follicle cells to stimulation by biologically active thyroid-stimulating hormone (TSH).

Decreased circulating thyroxine level · Frequent (79-30%)

A reduction below the normal concentration of thyroxine in the blood. Thyroxine (also known as T4) is the main hormone secreted by the thyroid gland into the blood. It can be converted into the active form triiodothyronine (also known as T3).

Increased circulating thyroglobulin concentration · Frequent (79-30%)

The concentration of thyroglobulin in the blood circulation is above the upper limit of normal.

Prolonged neonatal jaundice · Frequent (79-30%)

Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants.

Reduced radioactive iodine uptake · Frequent (79-30%)

A decreased amount of uptake on the radioactive iodine uptake (RAIU) test, which utilizes a radioisotope of iodine to measure how much iodine the thyroid gland absorbs from the blood. The radioactive marker is measured 4-6 hours and in some cases also 24 hours after administration of the radioactive marker.

Abnormal cry · Occasional (29-5%)

Any anomaly of the vocalizing of an infant's crying, i.e.,the typically loud voice production that is accompanied by tears and agitation.

Abnormality of epiphysis morphology · Occasional (29-5%)

An anomaly of epiphysis, which is the expanded articular end of a long bone that developes from a secondary ossification center, and which during the period of growth is either entirely cartilaginous or is separated from the shaft by a cartilaginous disk.

Bradycardia · Occasional (29-5%)

A slower than normal heart rate (in adults, slower than 60 beats per minute).

Compensated hypothyroidism · Occasional (29-5%)

Condition associated with a raised serum concentration of thyroid stimulating hormone (TSH) but a normal serum free thyroxine (FT4).

Constipation · Occasional (29-5%)

Infrequent or difficult evacuation of feces.

Delayed proximal femoral epiphyseal ossification · Occasional (29-5%)

Developmental delay of ossification of the proximal epiphysis of the femur.

Feeding difficulties in infancy · Occasional (29-5%)

Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.

Other findings in the same source

From: Orphanet

Additional reported features include Hyporeflexia (Occasional (29-5%)); Increased radioactive iodine uptake (Occasional (29-5%)); Large posterior fontanelle (Occasional (29-5%)); Lethargy (Occasional (29-5%)); Macroglossia (Occasional (29-5%)); Neonatal hyperbilirubinemia (Occasional (29-5%)); Thyroid hypoplasia (Occasional (29-5%)); Umbilical hernia (Occasional (29-5%)); Edema (Very rare (<4-1%)); Hypothermia (Very rare (<4-1%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Infancy; Neonatal

Inheritance in the source

From: Orphanet

Autosomal dominant; Autosomal recessive

Which doctor should you see?

The suggested department for discussing Hypothyroidism due to TSH receptor mutations is Endocrinology, with a endocrinologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which hormone or metabolic finding is important in this case?
• How should test timing and current medicines be taken into account?
• What follow-up would show whether the care plan is working?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Hypothyroidism due to TSH receptor mutations. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.