Ultrasound Images of Thyroid Dysgenesis and More

Link
Osler didn't have this fancy technology; doctors should be able to tell if half of something isn't there by sight and touch.

ICD Codes for Thyroid Disorders

http://www.icd9data.com/2009/Volume1/240-279/240-246/
Thyroid disorders
http://www.icd9data.com/2009/Volume1/240-279/240-246/243/default.htm
Congenital hypothyroidism
Myxedema

Resource: Werner and Ingbar's THE THYROID

Werner and Ingbar's THE THYROID is online at Google Books. This link leads to the chapter on Hypothyroid conditions.

BMJ - Genetics of Congenital Hypothyroidism

From the abstract:

Journal of Medical Genetics 2005;42:379-389; doi:10.1136/jmg.2004.024158
Copyright © 2005 by the BMJ Publishing Group Ltd.
REVIEW
Genetics of congenital hypothyroidism
S M Park1, V K K Chatterjee2

1 Department of Clinical Genetics, Addenbrooke’s Hospital, Cambridge, UK
2 Department of Medicine, University of Cambridge, Addenbrooke’s Hospital

Correspondence to:
Correspondence to:
Dr S M Park
Department of Clinical Genetics, Box 134, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, UK; soo-mi.park@addenbrookes.nhs.uk
Congenital hypothyroidism is the most common neonatal metabolic disorder and results in severe neurodevelopmental impairment and infertility if untreated. Congenital hypothyroidism is usually sporadic but up to 2% of thyroid dysgenesis is familial, and congenital hypothyroidism caused by organification defects is often recessively inherited. The candidate genes associated with this genetically heterogeneous disorder form two main groups: those causing thyroid gland dysgenesis and those causing dyshormonogenesis. Genes associated with thyroid gland dysgenesis include the TSH receptor in non-syndromic congenital hypothyroidism, and Gs and the thyroid transcription factors (TTF-1, TTF-2, and Pax-8), associated with different complex syndromes that include congenital hypothyroidism. Among those causing dyshormonogenesis, the thyroid peroxidase and thyroglobulin genes were initially described, and more recently PDS (Pendred syndrome), NIS (sodium iodide symporter), and THOX2 (thyroid oxidase 2) gene defects. There is also early evidence for a third group of congenital hypothyroid conditions associated with iodothyronine transporter defects associated with severe neurological sequelae. This review focuses on the genetic aspects of primary congenital hypothyroidism.

Abbreviations: ERSD, endoplasmic reticulum storage disease; NIS, sodium iodide symporter; PHP, pseudohypoparathyroidism; PPHP, pseudopseudo-hypoparathyroidism; PTH, parathyroid hormone; TPO, thyroid peroxidase; TRH, thyrotropin releasing hormone; TSH, thyroid stimulating hormone (thyrotropin)

Keywords: congenital hypothyroidism; candidate gene

Link to abstracthttp://jmg.bmj.com/cgi/content/abstract/42/5/379



Link to pdf

Hypothyroid and Alzheimer's - a connection?

Hypothyroid can not only cause dementia; this study suggests it is linked to Alzheimer's disease too.
http://pt.wkhealth.com/pt/re/clen/abstract.00003033-200012000-00012.htm;jsessionid=KBLSHYLsQBp2mqrqJ8Ttm4tsQXLVfpLc6kcfNyXXPVyXXGlL1YQT!-444506849!181195629!8091!-1
Given reliance on flawed American Thyroid level testing rather than on how the patient feels, prompt and appropriate treatment may not be delivered.

Peatfield was a general practitioner in the British National Health service who came to America and trained at the Broda Barnes Institute. He returned to England and started a thyroid private practice. His book summarizes over 25 years of clinical diagnosing and treating thyroid illness. One section of the book is devoted to the question, "Why thyroid blood tests can be unreliable".

Here is what Dr. Peatfield says:

"Anxiety in the medical establishment about rules and dogma has led to a slavish reliance on blood tests, which are often unreliable and can actually produce a false picture of the true situation"

"I have sadly come across very few doctors who can accept the fact that a normal, or low TSH, may still occur with a low thyroid."

"as a result of this test (TSH), thousands are denied treatment"

Peatfield lists several reasons why thyroid blood tests are flawed:

1) They measure hormone levels in the blood. What we really want to know is tissue levels, not blood levels.

2) The blood tests do not measure cellular receptor hormone resistance.

3) The blood tests do not measure conversion block. Some patients cannot convert their inactive T4 to active T3.

4) The thyroid tests do not account for adrenal insufficiency.

5) Paradoxical low TSH may occur with a low thyroid function.

These sentiments are shared by the teachings of Broda Barnes MD, and the Broda Barnes Foundation. However, Peatfield's book elaborates beyond the classic teachings of Broda Barnes by including chapters on the adrenal as well as a chapter on iodine supplementation. I found this book excellent, and it belongs in every medical library dealing with thyroid disease.

http://www.amazon.com/review/RSKEFGC2G8IZO

Thyroid Transcription Factors and Congenital Hypothyroidism

THYROID TRANSCRIPTION FACTORS AND CONGENITAL HYPOTHYROIDISM

Introduction
Primary congenital hypothyroidism (CH) is the most frequent endocrine-metabolic disease in infancy, with an incidence of about 1/3-4000 newborns. In about 85% of the cases, CH is caused by an alteration in the morphogenesis of the thyroid (thyroid dysgenesis, TD) (2). In 5-16% of cases TD it is associated with other major birth defects, mostly cardiac (Table 1) (3).
Most of the critical events in thyroid morphogenesis take place in the first 60 days of gestation in man or the first 15 days in mice. For this reason, thyroid developmental abnormalities result from morphogenetic errors during this period.
The regulation of formation, migration and proliferation of the thyroid gland are still largely unknown. Several genes, including those encoding thyroid specific transcription factors (TITF1, TITF2, PAX8), thyrotropin (TSH) and its receptor (TSHR), and/or other genes, have been demonstrated to play a role (1). Alterations in any of these genes can be responsible for thyroid dysgenesis.
Mutations in the genes involved in thyroid development give rise to animal models with TD, and mutations in the same genes have been identified also in a small number of patients with congenital hypothyroidism associated with TD.

In this review we will briefly describe the role of thyroid transcription factors and their involvement in the pathogenesis of TD.

NKX2-1/TITF1
NKX2-1, also known as TITF1 (Thyroid Transcription Factor–1) is a homeodomain transcription factor that was initially identified in a rat thyroid cell as a nuclear protein able to bind to specific sequences in the Tg promoter. TITF1 belongs to the Nkx2 class of transcription factors and is encoded by a gene, located on chromosome 14q13 (Table 1). The gene is formed by at least 3 exons and encodes for 42 kDa protein that is phosphorylated. During human development, the gene is expressed in the ventral diencephalon and in the telencephalon; in the lung bud and in the thyroid primordium (1, 4).
Studies in mice demonstrated that Titf1 is required for the survival and subsequent differentiation of the cells.

Link

Interesting... this is not a rare disorder. If an endocrinologist who mainly treats children cannot recognize this in adults, how will s/he recognize it in the young persons in his/her care?

Congenital Hypothyroidism - Diagnostics and Treatment

THYROIDAL CONGENITAL HYPOTHYROIDISM

B1. Ontogeny of the Thyroid Gland

The thyroid gland is the first endocrine gland to appear during embryonic development. The gland develops from a median endodermal thickening in the floor of the primitive pharynx. This placode (median anlage) develops into a diverticulum that grows caudally. By seven weeks of gestation, the human thyroid gland has usually reached its final site in the neck. Experiments with knock-out mice show that the transcription factors NKX2.1, FOXE1 and PAX8 are crucial for thyroid development. [76] Hypoplasia caused by inactivation of the TSH receptor is a later phenomenon.[77]

Defects in NKX2.1

The transcription factor NKX2.1 (TTF-1) is a member of a protein family essential for developmental processes. The NKX2.1 gene is localized on chromosome 14q13 and is expressed in thyroid, lung and several structures of the forebrain. Mice missing the NKX2.1 gene are stillborn, lack the thyroid gland, the pituitary gland, lung parenchyma, and show extensive defects in brain development.[78] Mutations in the NKX2.1-gene are not a frequent cause of CH but result in a syndrome combining a variable degree of congenital hypothyroidism, choreoathetosis, muscular hypotonia and pulmonary problems. [79] [80] [81] [82] The unfavorable outcome of these patients probably does not reflect the hypothyroid state but is most likely due to impaired NKX2.1 expression in the central nervous system. In mice NKX2.1 haploinsufficiency results in hypothyroidism caused by the concomitant reduced expression of the TSH-receptor. [83] Hypothyroidism can range from thyroid agenesis with severe hypothyroidism to a moderate hypoplastic gland with mild hypothyroidism to complete euthyroidism.

Thyroidmanager.org - U of Chicago course