B96 Thyroiditis, hypo and hyperfunction of the thyroid gland.

Question 1

What are the clinical types of thyroiditis and their causes?

Answer 1

Inflammation of the thyroid gland, with two clinical types.

1) With acute illness and severe thyroid pain, resulting from infection. Is uncommon.
* De Quervain Subacute granulomatous thyroiditis.
2) Main type: low level inflammation, no pain, and the manifestations are thyroid dysfunction.

• Hashimoto thyroiditis (aka chronic lymphocytic thyroiditis)
• Subacute lymphocytic thyroiditis (seen often as postpartum thyroiditis)

3) Rare forms of thyroiditis

• Riedel thyroiditis
• Palpitation thyroiditis

Question 2

Describe the symptoms and presentation of Hashimoto Thyroiditis

Answer 2

• aka Chronic Lymphocytic Thyroiditis
• Strong lymphocytic infiltration, with germinal center formation in the thyroid.
• Most common cause of hypothyroidism in developed world
• has Anti-Thyroperoxidase antibodies (Graves disease does not)
• is painless
• 20:1 female to male ratio
• Hypothyroidism develops gradually and may be preceeded by hyperthyroidism
• There is compensatory indreased TSH levels once hypothyroidism occurs
• Presents most often in women ages between age 45 and 65

Question 3

What is the histology of the itssue in Hashimoto thyroiditis?

Answer 3

lymphocyte infiltration and germinal center formation

Thyroid follicles are decreased in number, size, and atrophic.

Hurthle cell change, aka Oncocytic change aka Oxyphil cells with the epithelial cells having abundant pink cytoplasm from excess mitochondria. The epitheilail cells normally have a very pale/clear slightly basophilic cytoplasm.

There is increased connective tissue.

Question 4

What is the pathogenesis of De Quervain Thyroiditis?

Answer 4

aka Subacute Granulomatous Thyroiditis

• Caused by viral infection or postinfection inflammation, often preceeded by upper resp infection.
• Acute onset of pain, fever, malaise
• May** or **may not present with thyroid enlargement
• Transient hyperthyroidism followed by Transient hypothyroidism
  
  • ​caused by inflammation and hyperactivity and subsequent gland destruction/dysfunction, both that self resolve in a few weeks.
• serologic evidence of inflammation, leukocytosis elevated ESR.
• Spontaneous recovery in 6-8 weeks.

Question 5

What is the gross morphology of Hashimoto thyroiditis

Answer 5

Diffuse symmetric enlargement of the thyroid

In less common cases of the fibrosing variant, the thyroid is small and atrophic from extensive fibrosis and little inflammation/infiltration.

Gray/tan, firm on cut surface.

Question 6

What is the etiology of DeQuervain thyroiditis?

Answer 6

It is rare, seen in women more often, occurs usually between 30 and 50 years.

Question 7

What is the presentation, pathogenesis, and course of Subacute Lymphocytic Thyroiditis?

Answer 7

aka silent or painless thyroiditis

most likely autoimmune, and there are circulating antithyroid antibodies, in some patients presents after pregnancy as postpartum thyroiditis

causes a painless neck mass and transient thyrotoxicosis and then a abation of symptoms and retrun to normal.

it may cause mild symmetric thyroid enlargement, but often not.

There is lymphocytic infiltration and germinal center formation, but the whole disease is transient and resolves.

Thyrotoxicosis: hyperthyroidism due not to overproduction of T3 or T4, but from dsestruction and leakage of the hormones from the follicles.

nervousness, palpitations, rapid pulse, fatigability, muscular weakness, weight loss with good appetite, diarrhea, heat intolerance, warm skin, excessive perspiration, emotional lability, menstrual changes, a fine tremor of the hand (particularly when outstretched), eye changes, and variable enlargement of the thyroid gland.

Question 9

Describe Riedel thyroiditis

Answer 9

Rare disorder with unkown etiology

Extensive fibrosis of the thyroid and surrounding neck structures

Presents as a hard, fixed thyroid mass, seemingly like a thyroid carcinoma, but importantly, Riedel’s Fibrosing Thyroiditis occurs in young women, childbearing aged women, and thyroid carcinomas occur in the elderly.

Associated with idiopathic fibrosis in other body parts

Antithyroid antibodies are present

Riedel thyroiditis(RT) is generally a self-limited disease with a favorable prognosis. Death due to airway compromise is very rare in treated patients. Occasionally, spontaneous remission has been reported. Patients can also relapse.

In RT, morbidity is most frequently related to local compressive symptoms, such as dysphagia, dyspnea, hoarseness, and cough. Hypothyroidism is present in 30% of cases. Fibrotic invasion of adjacent anatomic structures may infrequently result in symptoms related to recurrent laryngeal nerve paralysis or hypoparathyroidism

Question 10

Describe palpation thyroiditis

Answer 10

Caused by heavy handed doctors vigorously palpating the thyroid gland.

Causes rupture/damage to thyroid follicles.

Inflammatory cell infiltrate with occasional giant cell formation.

Usually an incidental finding that does not cause clinical symptoms.

Question 11

What are the causes of hypothyroidism?

Answer 11

• Iodine deficiency #1 worldwide
• Hashimoto thyroiditis #1 in US and Eur, aka Autoimmune thyroiditis, aka chronic lymphocytic thyroiditis
• Panhypopituitarism from pit adenoma
• End stage Graves disease
• Iatrogenic
  
  • Radiation
  • Chemo
  • Thyroidectomy
  • Long term use of TSH secretion inhibitors and T3/T4 substitution, and sudden withdrawal.
  • Interferons, lithium
• Congenital agenesis or failure to descend (rare)
• Congenital lack or mutation of TPO (rare)
• Inflitrative destructive lesions
  
  • amyloidosis
  • lymphoma
  • scleroderma

Question 12

What is the clinical presentation of hypothyroidism?

Answer 12

Infants: cretinism

• severly stunted growth and mental retardation
• facial abnormalities, protruding tongue
• umbilical hernia
• used to be common in endemic iodine deficient areas
• now is more rare, and associated with enzyme defeiciencies of TPO and other enzymes.
• Iodine deficient cretinism mental retardation, is due to maternal deficiency, as her thyroid hormones cross the placental barrier and are critical for embryonic CNS development.

Adolescents and Adults:

• Myxedema
• Fatigue, apathy, and mental slowing are the main features.
• Droopy, tired face and periorbital edema
• Slurred speech
• Cold intolerance
• Weight gain
• cold, sweatless, pale skin
• bradycardia and low cardiac output
• Pericardial effusions are common and may cause heart failure.
• Constipation
• hyperlipidemia, hypercholesterolemia
• Non-pitting edema of the whole body, prominent in the periorbital region. From lots of ECM GAG deposition
• Macroglossia, same reason
• Hyperprolactinemia, elevated PRL secretion because TRH levels are high, (in attempt to stimulate T3 T4 secretion) and TRH weakly stimulate PRL release.

Question 13

How is hypothyroidism diagnosed?

Answer 13

Must measure both the T4 hormone itself, and TSH.

Elevated TSH occurs in primary hypothyroidism, hashimoto thyroiditis

Normal/Decreased TSH in people with hypothalamic disease or hypopituitarism

Serum T4 is always decreased and is by definition hypothyroidism.

Question 14

What are the causes of hyperthyroidism?

Answer 14

Diffuse toxic hyperplasia – Graves disease (most common)

Hyperfunctioning multinodular goiter

Hyperfunctioning adenoma

TSH‐secreting pituitary adenoma (rare)

transient acute stage of hashimoto thyroiditis

transient thyrotoxicosis in De Quervain subacute granulomatous thyroiditis

transient thyrotoxicosis in Subacute lymphocytic throiditis/postpartum thyroiditis

Question 15

Describe clinical presentation of Graves disease

Answer 15

aka Basedow disease

Most common hyperthyroidism

triad:

1. Thyrotoxicosis, with a diffusely enlarged hyperfunctional thyroid. Is always present.
2. Infiltrative ophthalmopathy causing swelling around the eyes and exopthalmos, protrusion of the orbits in 40% (not all!)
   
   • Has prominent lymphocytic infiltration and inflammatory edema of the perioribital region and extra-ocular muscles
   • there is also adipocyte infiltration of the periorbital redgion.
   • the inflammatory infiltration and edema of extra ocular muscles causes exopthalmos
3. Infiltrative dermopathy, aka pretibial myxedema seen in 1-5% of patients. Discoloration, inflammation, and lumpy swelling of the lower shins.

• it is important to note, the Infiltrative Opthalmopathy and the Infiltrative dermopathy are not due to T3 or T4 hyperthyroidism. Thats why these symptoms are not seen in general types of thyrotoxicosis. They are caused directly by the actions of TSH receptor stimulatin immunoglobulins stimulating TSH receptors on fibroblasts around the eye and in the pretibial region.

Question 16

What are the symptoms of hyperthyroidism/thyrotoxicosis?

Answer 16

Anxiety, hyperalertness

Fine tremor tremor of the hands.

Tachycardia, Palpitations

Widened pulse pressure, Systolic hypertension.

Diarrhea

Hyper-reflexia but with proximal muscle weakness

Warm, sweaty skin

Hair loss

Heat intolerance

Weight loss and increased apetite

Osteoperosis

Question 17

What is the etiology and pathogenesis of Graves disease?

Answer 17

• Peak incidence women between 20 and 40 years old.
• 7:1 female male ratio.
• Genetic factors important, HLA polymorphisms and CTLA-4 T cell inhibitory receptor polymorphisms.

The key driving factors of the disease are:

• Thyroid stimulating immunoglobulins (TSIs)
• and
• Thyroid growth stimulating immunoglobulins
• TSIs bind the TSH Receptor and induce release of T3/T4.
• TGSIs bind the same receptor, and stimulate the diffuse hyperplasia of the thyroid that is seen.

TSH-binding inhibitor immunoglobulins are also present in some cases and cause transient episodes of hypothyroidism.

Question 18

What is the gross morphology and histology of Graves disease?

Answer 18

Gross morphology:

Diffuse, symmetric hypertrophy, increased vascularization, with a smooth surface.

called a Diffuse Goiter.

Histology:

• Normal thyroid epithelial cells are cuboidal
• In Graves disease epithlial cells become taller and columnar, are more crowded, and produce epithelial papillary infoldings into the follicle.
• Around these hyperplastic epithelium is a colloid with scalloped margins, areas of clear vacuoles in the colloid near the epithelium due to increased processing by the epithelium.

In extra-thyroid tissues:

• There is a generalized lymphoid hyperplasia
• specifically in the periorbital region there is also GAG deposition and myxedema.

Question 19

Describe the pathogenesis of iodine deficient goiter

Answer 19

Iodine deficiency impairs T3 and T4 synthesis, decreases levels, increases TSH levels, causes thryoid hyperplasia and goiter.

The gland hyperplasia is may be to restore a euthryoroid state and function generate normal T3/T4 levels even at low iodine availability, or it may not, resulting in goiterous hypothyroidism.

Over time, a multinodular goiter occurs due to repeated cycles of iodine deficiency, high TSH, epithelial hyperplasia, then iodine availability, epithelial involution, and colloid nodules being left behind.

About 10% of these goiters over 10 years will develop autonomous nodules, that are secrete thyroid hormone independently of TSH stimulation. This is then called toxic multinodular goiter, or Plummer Syndrome. It causes hyperthyroidism that lacks the infiltrative opthalmopathy and pretibial dermopathy of Graves disease.

Question 20

What is the potentially fatal complication of Graves disease?

Answer 20

The Thyroid Storm

Abrupt onset of severe hyperthyroidism and hypercortisolism. Usually initiated by a stressor, surgery, childbirth.

1. Due to elevated catecholamines and massive hormone excess, usually in response to stress (e.g., surgery or childbirth)
2. Presents as arrhythmia and cardiogenic shock, hyperthermia, and vomiting with
3. Treatment is propylthiouracil (PTU), beta-blockers, and steroids
   i. PTU inhibits peroxidase-mediated oxidation, organification, and coupling
   steps of thyroid hormone synthesis, as well as peripheral conversion of T3 to T4

Question 21

What is the treatment for Graves disease?

Answer 21

Treatment is propylthiouracil (PTU), beta-blockers, and steroids

Question 22

Describe the gross morphology of iodine deficient goiter

Answer 22

Progresses through stages recurring stages, due to periods of iodine deficiency and iodine availability.

First, TSH induced hyperplasia creates a diffuse goiter,

Then, when iodine is again in the diet, and TSH levels drop, the hyperplastic epithelium undergoes involution, leaving behind a colloid goiter.

Repeated cycles cause many colloid goiter nodules to form, resulting in an assymetrically enlarged, multinodular goiter.