The Calgary Guide to Understanding Disease

Graves’ Disease: Pathogenesis and Clinical Findings B & T lymphocyte mediated autoimmunity attack TSH receptor -> Continuous stimulation of thyrotropin receptor by circulating autoantibodies -> Increased iodination of thyroglobulin, Thyroid gland hyperplasia Note: B & T lymph

Primary Hyperthyroidism - Pathogenesis and Clinical Findings Note: Although rare, gestational diseases can lead to thyrotoxicosis due to excess secretion of hCG, which is structurally similar to TSH. Secondary hyperthyroidism due to excess TSH production by the pituitary can a

Menstrual Cycle Physiology: the Uterine Cycle The endometrium has receptors for ovarian hormones! Changes in structure and secretory capacity of the endometrium occur in response to hormonal changes in the ovarian cycle. Note: The drop in progesterone concentration that trigger

Menstrual Cycle Physiology: Ovarian Cycle – Luteal Phase Explained • The LH surge can be thought of as only providing enough "battery power" for the corpus luteum to run and make progesterone for 14 days, which is why the luteal phase is a fixed length. • The timing and

Menstrual Cycle Physiology: Ovarian Cycle – Ovulation Explained Around Day 14, estrogen exerts sudden +++ positive feedback on the anterior pituitary (switch from negative to positive feedback poorly understood) -> surge in LH production and release LH causes: • Increas

Menstrual Cycle Physiology: Correlating the Ovarian and Uterine Cycles Note: Some charts show different relative levels of the gonadotropins (LH and FSH) to estrogen and progesterone, but the key is to compare the relative levels of estrogen with progesterone, and to observe ho

Menstrual Cycle Physiology: Ovarian Cycle – Follicular Phase Explained Early Follicular Phase (Days 0-5) • Granulosa cells secrete activin, a hormone that 1) Incr FSH production by pituitary, 2) Incr FSH receptors on granulosa cells, and 3) Decr theca cell androgen product

Menstrual Cycle Physiology: The Hypothalamic-Pituitary-Ovarian Axis Estrogen, when released: • Negatively feeds back on the hypothalamus and anterior pituitary to Decreased FSH production • Positively feeds back on the hypothalamus and anterior pituitary to Increased LH

Menstrual Cycle Physiology: Ovarian Cycle – Brief Overview LH and FSH are required for follicular development and continued growth until ovulation • Follicular Phase - Selection of dominant follicle - FSH from pituitary stimulates granulosa cells - LH from pituit

Pituitary Mass Effects - Pathogenesis and Clinical Findings • Pituitary turnors are almost always a benign adenoma. Pituitary adenomas are very common - approximately 1 in 6 individuals. These are usually asymptomatic and are found incidentally. Symptomatic pituitary adenomas

Growth Hormone Excess - Pathogenesis and clinical findings • Acromegaly and gigantism share the same pathophysiology but differ mainly in terms of time of onset of GH excess. GH excess prior to growth plate fusion -> gigantism. GH excess after growth plate fusion -> acromegal

Feedback Loop: Growth Hormone (GH) Growth Hormone: • Liver -> GHR activates JAK-STAT pathway -> Incr IGF1 • Bone - IGFIR activates osteoblasts and chondrocytes -> Incr ossification • Muscle -> GHR activates JAK-STAT pathway -> Incr gene expression/protein synthesis o

Feedback Loop: Prolactin (PRL) • PRL levels exhibit diurnal, menstrual, and age-related variation • TRH has a stimulatory effect on PRL release; however, dopamine is the principal regulator of PRL secretion Prolactin (PRL): • Hypothalamus -> Decr GnRH secretion -> De

21-Hydroxylase Deficiency (21-OHD): Pathogenesis and Clinical Findings Autosomal recessive mutation in CYP21A2 coding for the enzyme 21-OHase causes varying degrees of 21-OHD in the adrenal glands • Salt wasting crisis & hyperkalemia do not occur in utero as the placenta mai

Prader-Willi Syndrome: Pathogenesis and clinical findings • Maternal uniparental disomy: inheriting 2 copies of maternal chromosome 15 • Deletion of critical region on 15q11.2-13 gene on paternal chromosome ->Loss of parental copy of 15q11.2-13 ->Disruption of hypothalam